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SRC activates EGFR. 346 / 364
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"The increase in EGFR, Src and AnxA2 levels upon Her-2 downregulation and inhibition led us to investigate the role of AnxA2 in EGFR signaling in TNBC subset of breast cancer, where EGFR plays a major role in survival, growth, migration and invasion of cancer cells XREF_BIBR, XREF_BIBR, XREF_BIBR, XREF_BIBR."
22957061
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"Src kinases mediate the EGFR transactivation induced by Bn-analogue and NT in BON cells."
23220008
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"Regardless how Src is activated by GPCR, it is important to determine how Src activates EGFR, the activation status of Src-activated EGFR, and the effects of Src-activated EGFR on the downstream signaling cascades and cell functions."
26771606
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"Present data also suggest that only a portion of the intracellular EGFR, Src and Stat3 protein pools are utilized in the formation of the nuclear complex, raising the possibility that there may be diverse cellular pools of EGFR, Src, or Stat3 with different accessibility limitations."
21573184
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"In response to PGE 2 stimulation, the EP2 receptor recruits beta-arrestin 1 to phosphorylate tyrosine protein kinase Src, which in turn activates EGFR, leading to activation of PI3K and Akt and Ras and ERK pathways, which together promote tumor cell activities (XREF_FIG) [XREF_BIBR, XREF_BIBR]."
23796953
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"Following ouabain binding, the Src kinase domain releases from Na + / K + -ATPase and activates the EGFR forming a cardiotonic steroid receptor intracellular signaling pathway."
33716756
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"It should be noted that Src can induce activation of EGFR by direct phosphorylation on Tyr 845."
26444028
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"Furthermore, combined inhibition of PLCgamma1 and c-Src abrogates EGFR mediated head and neck squamous cell carcinoma invasion [XREF_BIBR]."
26811493
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"In this study, we investigated (1) whether Src mediates epidermal growth factor receptor (EGFR) transactivation; (2) if ERK1/2, PI3Kdelta and Akt and NF-kappaB are signaling effectors downstream of Src and EGFR activation; and (3) if upstream inhibition of Src and EGFR is more effective in downregulating the allergic inflammation than selective inhibition of downstream signaling pathways."
28855674
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"Our results present a novel mechanism by which the PI3K and Src signaling cascades cooperate to activate Rac and promote intestinal epithelial cell migration downstream of EGFR."
17991704
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"Overall, these findings, together with c-Src-dependent EGFR transactivation, suggest that NAGLU deficient cardiomyoblasts develop a hypertrophic phenotype through a coordinated intracellular and extracellular EGFR activation induced by c-Src and HB-EGF, respectively."
29348482
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"We recently reported that ANG II-mediated tubulointerstitial fibrosis is mediated by src-dependent epidermal growth factor receptor (EGFR) activation."
22169008
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"This Src and SHP -2 activation mediates EGFR transactivation that causes Ras/Raf/ERK signaling cascade activation."
16414009
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"Indeed, Yan et al. 7 demonstrate that inhibition of Src kinase by PP1 blocks the activation of EGFR and STAT3, both of which have been implicated in facilitating kidney fibrosis."
26759038
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"In resistant cell lines, Src silencing moderately inhibited EGFR related transducers, but efficiently reduced Src activation."
24887236
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"TGF-beta expression can be regulated by sustained EGFR dependent signaling, which is activated by the ROS dependent phosphorylation of Src due to the Ang II receptor activation [XREF_BIBR]."
27331812
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"Outcomes remained dismal stemming from mechanisms of resistance particularly the nuclear cycling of EGFR, which is enhanced by Src activation."
32295603
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"Besides gene mutation, multiple resistance mechanisms to cetuximab include overexpression of EGFR ligands and receptors, ubiquitylation, translocation of EGFR, EGFR variant III, modulation of EGFR by SRC family kinases, and transactivation of alternative pathways that bypass the EGFR pathway [XREF_BIBR]."
24714091
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"The TNF-α-induced activation of the extracellular signal-related kinase/guanine nucleotide exchange factor H1/ras homolog family member A pathway in tubular cells is mediated through Src- and TNF-α convertase enzyme-dependent EGFR activation."
29693180
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"The role of zinc in cellular signalling seems to include effects on growth-factor-mediated induction of gene expression [14], Src mediated activation of EGFR [51], insulin like growth factor-1 (IGF1)-[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
19246244
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"In addition to this so-called canonical AHR pathway, the ligand-driven dissociation of the cytosolic multiprotein complex may result in the activation of the tyrosine kinase c-Src, which subsequently can activate epidermal growth factor receptor (EGFR) and downstream mitogen-activated protein kinase (MAPK) signal transduction ( xref ) [ xref , xref , xref ]."
31795255
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"Given that c-Src is required for EGFR internalization and signaling, and that active c-Src may induce ligand independent EGFR activation 49, inhibition of c-Src might also impede EGFR signaling events in NAGLU defective cells as well as in other cells lacking a lysosomal enzyme involved in GAG metabolism."
29348482
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"Supplementary Fig. 1 Autonomous Src activation does not trigger autocrine production of EGFR ligands."
20832399
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"Because Src can activate EGFR via the direct phosphorylation at Tyr-845 (Biscardi et al. xref ), we evaluated the effects of OVA on the phosphorylation of this residue in EGFR."
25505586
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"On the other hand, SP dependent phosphorylation of HER2 and EGFR decreased substantially in the presence of the MMP inhibitor 1-10, phenanthroline monohydrate, and the dual inhibition of both c-Src and MMP almost abolished the activation of HER2 and EGFR."
26114632
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"We also show that MMP independent EGFR activation is essential to the sustained phase of the protease response, and that Src kinases may mediate EGFR transactivation."
28671992
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"Inhibition of calcium/calmodulin dependent kinase II (CaMKII), phosphatidylinositol 3-kinase (PI3K), and Src, however, did block EGFR transactivation by alpha1A-AR and alpha1D-AR."
23902938
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"Because Src can activate EGFR via the direct phosphorylation at Tyr 845, we evaluated the effects of OVA on the phosphorylation of this residue in EGFR."
25505586
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"Src was constitutively activated (XREF_FIG), and constitutively enhanced yet EGFR kinase activity dependent EGFR-Src interactions (XREF_FIG) were observed in mutant EGFR- but not wtEGFR expressing cells."
19305428
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"We have recently shown, in both asthma and diabetes disease models, in which EGFR activity is enhanced, that inhibition of Src kinase reduces EGFR transactivation and ameliorates the disease features [4, 42, 43]."
31675376
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"Since EGFR inhibition was effective on stiff but not on soft pillars, and EGFR activation through Src was force-dependent, we hypothesized that Src-dependent activation of EGFR was required for rigidity sensing."
28459445
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"For IL-1β, Src-dependent EGFR activation was also described with respect to IL-1β-induced matrix metalloproteinase-9 (MMP-9) expression in A549 cells [ xref ]."
34205482
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"Since PI3K generates the D-3 phospholipid PIP 3 to activate the serine/threonine kinase Akt, we wanted to exclude the possibility that Akt rather than PI3K was phosphorylating Src to promote EGFR transactivation."
27169346
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"Thus it seems that the down-regulation of ROCK/LIMK/cofilin pathway may be an essential event of the ouabain induced cell swelling.The present study demonstrates that cofilin dephosphorylation by ouab[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
16713181
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"We therefore suspected that EGFR activation by heparanase is similarly mediated by Src and examined this possibility by exposing heparanase transfected U87 (XREF_SUPPLEMENTARY, upper two panels) and A431 (XREF_SUPPLEMENTARY, lower two panels) cells to specific inhibitors of key signaling molecules."
19074873
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"Supplementary Fig. 3 In contrast to the strong ligand independent EGFR activation by Src, EGF induces concentration dependent EGFR degradation."
20832399
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"In turn, FAK triggered Src activation and Src mediated EGFR transactivation resulting in STAT3 signaling."
29036202
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"Dsg2 is required for EGFR localization at intercellular junctions as well as for Src mediated EGFR activation."
29980799
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"These findings indicate that c-Src activates the EGFR and MAPK pathway in NSCLC cells and cooperates with loss of DUSP6 to activate ERK1/2 after EGFR inhibition."
26453958
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"The unique pathway elucidated here in which c-Src and PI3K are sequentially activated downstream of the EGF receptor may serve as a prototype of signaling mechanisms by GnRHR and by additional GPCRs in various cell types."
12750372
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"We now present data that Src family kinases (SFKs) are highly activated in cetuximab resistant cells and enhance EGFR activation of HER3 and PI (3) K/Akt."
19276677
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"Src modulates the function of EGFR through phosphorylation of tyrosine residues on EGFR that allow for coupling to downstream signaling events [XREF_BIBR, XREF_BIBR]."
30895346
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"Since c-Src has also been reported to activate metalloproteinases, releasing EGFR ligands following stimulation by GPCRs, we examined whether c-Src mediates extracellular release of EGFR ligands."
17349623
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"In addition, butaprost stimulation of EP2 led to EP2-β-arrestin1 complex formation with subsequent Src activation and transactivation of EGFR and down stream effectors."
| PMC
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"Evidence to date supports a model wherein c-Src potentiates the survival, proliferation and tumorigenesis of EGF receptor family members, in part by associating with them."
11250711
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"These observations indicate that SRC hyperactivity in TZMB-resistant BC cells promotes a positive feedback cycle where SRC activates EGFR, HER2, and HER3 which, in turn, can activate SRC."
22482061
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"Interestingly, it is now well-established that during GPCR/G i signaling, Gβγ release can activate a myriad of effectors to modulate diverse signaling pathways downstream of GPCRs, including Src, which in turn activate EGFR to promote ERK1/2 activation ( xref , xref , xref )."
31920979
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"Transactivation of EGFR by angiotensin II (AngII), ET-1, or bradykinin involves ROS dependent activation of c-Src, which then activates EGFR and leads to ERK activation and pro growth signaling [XREF_BIBR - XREF_BIBR]."
24132149
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"C-Src activates EGFR by phosphorylation on residue Tyr845 XREF_BIBR that is located in the activation loop of the catalytic domain."
21152443
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"Indeed, by using a combination of small molecule inhibitors and dominant negative approaches it has been found that PLCgamma1 and c-Src activation contributes to head and neck squamous cell carcinoma [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
23925006
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"The tyrosine phosphatase PTPRO sensitizes colon cancer cells to anti-EGFR therapy through activation of SRC mediated EGFR signaling."
25301722
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"Together, this data indicates that SRC, GRIP1, and RAB9A normally mediate KIF5B-RET-mediated switching of EGFR from predominantly phospho-Y1068 to predominantly phospho-Y845, that is, switching from an ERK associated phosphorylation event to a SRC associated event."
28877471
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"EGFR can also be activated in a ligand independent manner by cellular Src (c-Src), a non receptor tyrosine kinase."
22834827
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"This observation indicates the requirement of the prosurvival form of Fas for the formation of a signaling platform where Src, Yes-1, and STAT3 may couple the pro survival signal of Fas to EGF induced EGFR signaling."
30127519
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"We previously showed that exposure to metal-laden PM inhibits protein tyrosine phosphatase (PTP) activity in human primary bronchial epithelial cells (HAEC) and leads to Src dependent activation of EGFR signaling in B82 and A431 cells."
16410015
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"We conclude that CCh stimulated EGFr transactivation and subsequent ERK activation, a pathway that limits CCh induced chloride secretion, is mediated by metalloproteinase dependent extracellular release of TGF-alpha and intracellular Src activation."
12202486
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"In contrast, EGFRvIII + tumors were driven by activation of the prototypical Src family kinase c-Src that promoted VEGF secretion leading to angiogenic tumor growth."
27286795
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"To our knowledge, the present study is the first to provide evidence that activation of EGF receptor by the primary ligand EGF evokes Ca 2+ sensitization in VSMCs by Rho-kinase-mediated inactivation o[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
26004531
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"Other mechanisms that lead to cetuximab resistance include amplification of MET, XREF_BIBR overexpression of IGF1R, XREF_BIBR overexpression of EGFR ligands and receptors, such as ErbB2 XREF_BIBR and amphiregulin, XREF_BIBR modulation of EGFR by Src family kinases, transactivation of alternative pathways that bypass the EGFR pathway, such as MET and IGFR, ubiquitination, expression of EGFR variant III, and induction of EGFR translocation."
27099521
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"These data indicate that SRC activation induces trastuzumab resistance by facilitating EGFR, ERBB2 and HER3 activation in TtzmR cells."
21399647
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"Genetic and pharmacologic inhibition of Src and Fyn block EGFR dependent motility and tumor growth in vitro and in vivo."
19690143
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"Notably, TNF-α induces ADAM17 and Src dependent EGFR activation and initiates the extracellular signal-regulated kinase (ERK)-dependent guanine nucleotide exchange factors (GEF)-H1 and RhoA signaling pathway, suggesting a mechanistic link between inflammatory and proliferative pathophysiology [ xref ]."
33575814
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"Activated Src induces EGFR surface down-regulation via clathrin coated vesicles by sequestration into recycling endosomes without accelerating degradation, raising the possibility of sustained EGFR en[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
20832399
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"SRC family tyrosine kinases in wound- and ligand induced epidermal growth factor receptor activation in human corneal epithelial cells."
16799022
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"While Src signaling and function relies heavily on the endosomal system, Src also modulates components of the endocytic pathway by controlling the internalization and trafficking of the very receptors which activate it (EGFR, FGFR, integrins)."
25372749
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"This pathway involved the receptor mediated activation of a pertussis-toxin sensitive G protein (presumably G i/o), G betagamma -mediated activation of Src and phosphorylation of Shc, resulting in matrix mettaloproteinase mediated release of HB-EGF and transactivation of the EGFR."
19442754
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"Similarly, although SRC is sufficient to activate PI3K signaling (as observed with inducible v-SRC expression, XREF_SUPPLEMENTARY), SRC inhibition with dasatinib did not abolish feedback activation of EGFR or PI3K (XREF_FIG, data not shown)."
23774212
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"Potentiation of epidermal growth factor receptor mediated oncogenesis by c-Src : implications for the etiology of multiple human cancers."
7542783
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"Src activation enhances EGFR activation and downstream PI3K-Akt signaling."
22153719
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"Src mediated EGFR transactivation is not required for Akt activation triggered by T. gondii but mediates ROP16 independent STAT3 activation."
29036202
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"In 2006, Lee at al., showed that TNF-alpha induces the expression of MMP-9 by Src mediated EGFR, PDGFR/PI3K/Akt signaling pathway in human tracheal smooth muscle cells [XREF_BIBR]."
27245276
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"In conclusion, by promoting destruction of c-Cbl, c-Src enables EGFR to evade desensitization, which explains Src-EGFR collaboration in oncogenesis."
12604776
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"Src may activate MMP causing the metabolism of EGFR precursor ligands to biologically active TGFalpha."
25761747
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"A high level of Src activates the downstream of the signal pathway of EGFR without combining ligand."
23226426
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"Inhibition of Src and Abl kinases with the dual specificity drug saracatinib suppressed EGFR activation and ECM degradation in HNSCC, suggesting that Src is responsible for mediating the pro invasive signals resultant from imatinib mediated Abl family kinase inactivation."
23146907
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"Interestingly, Src has been shown to induce EGFR transactivation and production of TGF-beta1 in response to stimulation with angiotensin II [XREF_BIBR]."
29137389
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"Thus, T. gondii promotes its survival through sustained EGFR signaling driven by PKCalpha/beta-> Src, and inhibition of EGFR controls pre-established toxoplasmosis."
31290228
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"Rescue experiments demonstrated that overexpression of EGFR, activated Src or caveolin in NPC cells all resulted in reversal of YC-1-induced inhibition of cellular invasion, with EGFR and activated Sr[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
19879857
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"In this regard, estrogens were shown to trigger through GPER the SRC mediated extracellular release of heparan bound EGF and then the activation of EGFR in ER negative BC cells."
33364239
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"Mechanistically, inhibition of Src by PP1 appears to disrupt TGFbeta1 and Smad3 and epidermal growth factor receptor (EGFR) signaling, 2 key signal pathways that have been implicated in renal fibrogenesis."
26759038
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"As can be seen in XREF_FIG, under both high and low levels of EGF, the overexpression of Src (i.e., mutating Src to be constitutively-active) leads to the decrease of the activity levels of the node representing EGFR homodimers on the plasma membrane, while increasing the% ON levels of nodes representing the receptor during the internalization process."
23637902
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"This leads to c-Src activation and stimulation of the epidermal growth factor receptor (EGFR), which evokes phosphatidylinositol 3-kinase-dependent production of phosphatidylinositol (3,4,5)-trisphosphate and, in turn, activates Rac1 subunit of NADPH oxidase."
21777669
sparser
"EGFR can also be activated in a ligand-independent manner by cellular Src (c-Src), a non-receptor tyrosine kinase."
31877856
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"Thus, our study raises the possibility that Src activates PI3K, although the specific mechanism for this effect remains to be determined.For certain GPCRs, Src has been shown to induce EGFR transactivation, stimulate the PI3K-Akt pathway, and activate the ERK1/2 cascade (43, 48, 70)."
31920979
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"Conversely, Src induced EGFR transactivation and PI3K activation lead to the activation of RAC1, an essential event in the activation of NOX 101."
31591535
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"Tesevatinib (KD019) is a novel, oral, reversible TKI, which inhibits EGFR, HER2 and neu, and Src family nonreceptor tyrosine kinases."
30018881
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"Src then causes the activation of the epidermal growth factor receptor, which results in the phosphorylation and activation of the ERK MAPK and the cAMP response element binding protein transcription factor."
21177760
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"Src can activate EGFR either directly through the phosphorylation of EGFR at Tyr 845 in the cytoplasm, or indirectly via the metalloproteinase catalyzed release of HB-EGF from pro-HB-EGF."
25505586
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"For instance, Src often interacts with EGFR and mediate EGFR-associated events [22]."
30285892
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"Here, we show that the association of Src and TACE at the cell membrane mediates ectodomain shedding of EGFR ligands and is an important mechanism of EGFR transactivation."
24520077
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"This process is mediated by ligand induced EGFR activation leading to subsequent phosphorylation and activation of protein tyrosine kinases Src and FAK."
24709902
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"These observations indicate that SRC hyperactivity in TZMB resistant BC cells promotes a positive feedback cycle where SRC activates EGFR, HER2, and HER3 which, in turn, can activate SRC."
22482061
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"Also, Src family kinase activation of epidermal growth factor receptor [EGFR, or human epidermal growth factor receptor (HER2)] activity is needed to continue spreading and polarization as well as for rigidity sensing."
30403543
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"Transforming growth factor- β (TGF- β ) signaling by TGF- β receptor (through Smad2/3 pathway), Src-dependent epidermal growth factor receptor (EGFR) activation, and NADPH oxidase-induced elevation of reactive oxygen species formation promote Ang II-induced VSMCs proliferation [ xref , xref , xref ]."
30186848
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"We thus tested whether Src mediates TGF-beta-induced EGFR transactivation."
28943431
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"Together, these studies suggest that either (i) the concentration of PP2 did not completely inhibit Src activation, or (ii) PP1 may inhibit kinases other than Src and that non Src pathways also trigger EGFR activation."
20584561
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"While ligand shedding probably activates the same signaling cascades as soluble ligands, c-Src-activated EGFRs are phosphorylated on a unique subset of tyrosine residues with markedly distinct physiological outcomes ( xref )."
28088463
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"When AKAP121 is transfected, Src dependent activation of the EGF receptor is diminished because PTPD1 is recruited to mitochondria [XREF_BIBR]."
21355846
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"The EGFR ubiquitination/degradation and Src activation was identified as a resistance mechanism to cetuximab in DiFi colorectal cancer cells ."
20444542
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"Such a direct EGF effect, including the Src triggered EGFR transactivation may also hold true for zyxin, since we have also seen significantly lower levels of this FA constituent at FA sites in the pr[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
26079101
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"SRC kinases also provide protection from AKI, and contribute to tissue regrowth [XREF_BIBR, XREF_BIBR]; at least part of this protective activity may reflect SRC dependent stimulation of EGFR pathway activity [XREF_BIBR]."
31830556
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"This effect was mediated by ligand induced epidermal growth factor receptor (EGFR) activation and the subsequent phosphorylation of Src and FAK."
19147560
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"Intracellular, Src mediated EGFR transactivation was hypothesized to be one potential mechanism by which trypsin increases TER in SCBNs."
28671992
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"It is remarkable that the model could make an accurate de novo prediction that the elevated Src activity will promote the localization of EGFR in internal compartments of the endocytic pathways even in the absence of added ligand."
23637902
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"We cannot exclude that the effects of mTOR inhibition on SRC and ERK activity occur via separate pathways; anyway, ERK inactivation could be the result of SRC-mediated EGFR delocalisation, positioning all the actors in one integrated route."
32823532
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"Src mediated EGFR transactivation contributes to a survival response following oxidative injury."
15075181
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"It appears that MDA-9 and Syntenin overexpression activates c-Src, which in turn upregulates EGFR by phosphorylation at Tyr 845 with concomitant activation of PI3K and AKT and resulted in increased proliferation."
23873690
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"Stimulation of cells with EGF revealed that c-Src traffics into the cell with activated EGFR and that c-Src expression and kinase activity prolongs EGFR activation."
18448311
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"Further investigations of this model of acquired resistance to cetuximab indicated that Src family kinases (SFKs) are highly activated in cetuximab resistant cells and enhance EGFR activation of HER3 and PI (3) K/Akt."
19028347
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"Another study reported that C-X-C motif chemokine 12 (CXCL12)/CXCR4 signaling transactivates EGFR through the activation of proto-oncogene c-Src in breast cancer cells; the activation of EGFR also upregulates CXCR4 transcriptionally via the increased expression and activity of hypoxia inducible factor 1alpha (HIF-1alpha)."
28356948
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"These results indicate that TNF-alpha production by TCDD in differentiated THP-1 macrophages is AhR dependent and involves activation of EGFR and ERK, but not c-Src, JNK, nor p38 MAPK."
17934341
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"It is therefore difficult to address the question of Src mediated EGFR kinase activation in any cell that coexpresses EGFR and one of its heterodimer partners, ErbB2 or ErbB4.The Src and EGFR tyrosine[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
12648464
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"Previous reports demonstrate Src is frequently activated downstream of GPCR activation in cancer cell lines [XREF_BIBR], and evidence suggests that Src can directly activate the intracellular domain of the EGFR [XREF_BIBR] as well as play a role in MMP activation [XREF_BIBR]."
24718936
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"This leads to c-Src activation and stimulation of the epidermal growth factor receptor (EGFR), which evokes phosphatidylinositol 3-kinase-dependent production of phosphatidylinositol (3,4,5)-trisphosphate and, in turn, activates Rac1 subunit of NADPH oxidase. xref Nox4 and Nox5 do not require p47 phox or Rac1 subunits. xref Thus, in vascular cells, AngII primarily increases activity of Nox1 or Nox2 ( xref ). xref Activation of c-Src is redox sensitive and stimulated by H 2 O 2 , xref which appears to represent a feed-forward mechanism whereby H 2 O 2 -mediated activation of c-Src amplifies NADPH oxidase activity of Nox1 and Nox2."
21777669
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"In contrast, Src-dependent EGFR activation was found in response to PV-IgG containing antibodies against Dsg3."
31178865
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"It is known, for instance, that EGFR (epidermal growth factor receptor) can be activated by src without the presence of the EGFR ligand and that there is a direct correlation between EGFR overexpression and src activation [59]."
31861445
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"However, in the present study, we showed that guggulsterone caused robust proliferation of two human colon cancer cell lines through Src mediated activation of EGFR and post-EGFR signaling."
23119029
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"Previous studies have shown that Src mediates EGFR transactivation in response to physical stimuli and some active substances such as Ang II."
26444028
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"The Src and EgfR module includes Src dependent activation of EgfR; if either component is missing from the initial state, signaling along this cascade is compromised."
19317917
signor
"In summary, this study describes a novel mechanism for metal-induced egfr transactivation, which is likely to be mediated by src through the phosphorylation site of tyr-845 on egfr. emanating from a variety of growth factor receptors, including egfry845 (e-e-k-e-y845-h-a-e)"
11983694
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"In addition, we investigated whether EGFR activation by diesel exposure could be mediated by Src activation and phosphorylation of Src Tyr 416 and leading to transactivation of EGFR at Tyr 845 and whether activation of EGFR would increase the downstream MEK-ERK pathway signalling, linked to proliferation and differentiation."
18460189
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"We demonstrated previously that EGFR deficient murine embryonic fibroblasts showed decreased activation of c-Src following stimulation with GRP where c-Src was shown to mediate the cleavage of EGFR pro ligand cleavage."
18594011
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"Since EGFR transactivation is reportedly promoted by Src (18,24), the effects of PP2 (300 nM, a Src family tyrosine kinase inhibitor) were also examined."
17433115
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"This suggests that Src mediates EGF receptor (EGFR)-dependent regulation of the Hippo pathway, even though we previously reported that the Src inhibitor PP2 did not block the effect of EGF on YAP."
26216901
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"One of this pathways might include c-Src dependent EGFR and MAPK activation."
12162444
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"YES also phosphorylates upstream regulators of RAS and MAPK signaling, including EGFR, SHC and SHP2, which were not targeted by SRC due to the absence of palmitoylation."
26269757
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"Transient knockdown of Src in FG cells disrupted EGFR mediated Rap1-GTP loading (XREF_FIG) and blocked migration on vitronectin (XREF_FIG), but not on collagen (data not shown) suggesting Rap1 activation by EGFR was Src dependent."
21963850
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"In addition, butaprost stimulation of EP2 led to EP2, beta, and arrestin1 complex formation with subsequent Src activation and transactivation of EGFR and down stream effectors."
| PMC
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"For example, does Src stimulates the dimerization of EGFR?"
26771606
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"C-Src activation induced by EGFR ligands mediates the binding of phosphatidylinositol 3-kinase (PI3K) to EGFR, leading to AKT phosphorylation and, in turn, induction of survival and migration signalling pathways (Franke et al., 2003; Shien et al., 2004; Jiang et al. 2003)."
35059624
sparser
"Also, Src family kinase activation of epidermal growth factor receptor [EGFR, or human epidermal growth factor receptor (HER2)] activity is needed to continue spreading and polarization as well as for rigidity sensing ( xref )."
30403543
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"Our recent studies indicating a direct association between DUOX1 and Src in response to ATP stimulation suggest a direct role for DUOX1 in oxidative Src activation in EGFR transactivation, 21 and our [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
26597162
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"Our results also demonstrate that activation of Src kinases is important in mediating EGFR transactivation in BON cells, because we found that EGFR activation induced by NT or the Bn-analogue, is completely inhibited by the specific Src kinase inhibitor, PP2, but not by a inactive related compound, PP3."
23220008
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"Using both small-molecule EGFR inhibitors and EGFR shRNA, we investigated the mechanism of EGFR activation in cardiomyocytes and concluded that c-Src mediated the EGFR activation induced by Ang II."
26762600
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"In conclusion, the present study indicated that SRC mediates EGFR activation through the formation of SRC and EGFR heterodimers, and that activated EGFR stimulates ERK and Akt pathways in CXCL12 and CXCR4 induced gastric cancer cell migration."
28781651
sparser
"It is known, for instance, that EGFR (epidermal growth factor receptor) can be activated by src without the presence of the EGFR ligand and that there is a direct correlation between EGFR overexpression and src activation [ xref ]."
31861445
sparser
"It is known that EGFR can be activated by Src kinase (Src) ( xref ) and that both Src and EGFR are involved in the development of PAH ( xref , xref )."
31298924
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"Angiotensin II induced growth of vascular smooth muscle cells requires an Src dependent activation of the epidermal growth factor receptor."
10916078
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"At the top of the ERBB signaling cascade, SRC phosphorylation of EGFR on residue Y845 in the catalytic domain stabilizes kinase activation, and on Y1101 in the C-terminal tail promotes EGFR binding to SHC [XREF_BIBR]; SRC also enhances EGFR activation of the JAK-STAT pathway [XREF_BIBR] (see Weimbs review)."
31830556
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"Non-toxic Src inhibition could reverse the diffusive properties of the EGFRvIII/EGFRwt population in U87 model and patient-derived GBM cells."
32024816
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"Like low EGF concentrations, activated Src triggered EGF-R endocytosis via clathrin coated vesicles and led to its sequestration in perinuclear and recycling endosomes with avoidance of multivesicular bodies and lysosomal degradation."
22438768
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"Similarly, Src-activated Epidermal Growth Factor Receptor (EGFR) signals through Ras-MAPK to engender phosphorylation of the E-box binding transcription factor USF and facilitate its interaction with activated Smad2/3 to regulate PAI-1 gene expression [ xref ]."
22204556
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"Our mutagenesis data suggest that Act1-Src interaction via the SH3 domain facilitates the recruitment of Src to the IL-17R, Act1, and EGFR complex, providing a potential mechanism by which Src can be engaged in the IL-17RA and EGFR complex to mediate transactivation of EGFR in an IL-17A-dependent manner."
30578323
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"9 In addition to ligand dependent mechanisms, EGFR can be directly activated by Src phosporylation on Tyr 845."
26312153
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"Conclusion : O 3 exposure increased IL-8 expression through Src mediated EGFR transactivation in HBEC."
25303742
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"MBG, NKA, and Src complex activates of epidermal growth factor receptor (EGFR) signaling resulting in a degradation of Fli1 (a negative nuclear regulator of the procollagen-1 gene) and induction of collagen-1 synthesis (XREF_FIG)."
27884238
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"PP2 inhibition of SRC suppressed the migration ability and activation of EGFR."
28781651
reach
"XREF_BIBR, XREF_BIBR In line with these observations, our current study showed that Src mediates EGFR transactivation after UUO injury (see below) and triggered renal epithelial cells arrest at the G2/M phase of the cell cycle."
26444028
reach
"Inhibition of Src or out competing endogenous Src with a dominant negative mutant inhibited EGFR endocytosis by approximately 50%."
29885323
reach
"Our findings suggest that activated forms of Src might stimulate the EGFR and ERK in the Src expressing tumor cells as well as in surrounding non transformed stromal cells by activation of ADAM17 and release of ligands of the EGFR."
20871631
reach
"EGFR signaling is augmented by Src family kinases, but the mechanism is poorly understood."
26551075
signor
"The c-terminal autophosphorylation domain of egfr was extensively phosphorylated by c-src./These studies revealed that y1086 was phosphorylated to a significantly higher extent by c-src than by egfr. Additionally, y1101 was identified as a unique c-src phosphorylation site."
8845374
reach
"Our finding that Src is an important transactivator of EGFR in asthma, therefore leads us to speculate that SFK may be a signaling hub and relay transducing pathways that could lead to airways inflammation, remodeling and AHR."
28855674
reach
"Notably, co-targeting Src and IGF-1R effectively suppressed the colony formation of EGFR TKI resistant NSCLC cells (H1975, PC-9/GR and PC-9/ER) [XREF_BIBR] (Additional file 18 : Figure S17D)."
26041671
reach
"Src dependent tyrosine phosphorylation regulates dynamin self-assembly and ligand induced endocytosis of the epidermal growth factor receptor."
12011079
reach
"Src mediated ligand independent activation of EGFR."
28459445
reach
"Our recent studies indicating a direct association between DUOX1 and Src in response to ATP stimulation suggest a direct role for DUOX1 in oxidative Src activation in EGFR transactivation, and our observation of DUOX1 dependent cysteine oxidation of EGFR may imply a similar direct role for DUOX1 in regulating EGFR activation."
26597162
sparser
"Thus, Src-activated EGFR colocalized with integrin clusters at peripheral adhesions only when they were under force."
28459445
reach
"Regardless how Src is activated by GPCR, it is important to determine how Src activates EGFR, the activation status of Src activated EGFR, and the effects of Src activated EGFR on the downstream signaling cascades and cell functions."
26771606
reach
"To further complicate matters, active Src may also activate TACE and ADAM17 and lead to ligand dependent EGFR activation [XREF_BIBR]."
19041864
reach
"O3 exposure increased IL-8 expression through Src mediated EGFR transactivation in HBEC."
25303742
reach
"The difference between short-term and long-term Src exposure could also explain why our observations appear opposite to previous reports using fibroblasts either stably overexpressing or defective in [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
20832399
eidos
"C-Src modulates epidermal growth factor receptor ( EGFR ) activation and amplifies its downstream oncogenic signals ."
32517369
reach
"In addition, active Src family kinases can feed back to activate EGFR XREF_BIBR - XREF_BIBR."
32245944
reach
"G1 induces endothelium dependent vasorelaxation through Src mediated activation of the EGF receptor and the Akt pathway in rat aorta."
24028616
reach
"The above results indicated that thrombin can modulate the phenotype by regulating nestin expression in rat VSMCs.Previous studies have revealed that the PAR induced EGFR transactivation leading to pr[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
19245830
reach
"Since Src can mediate EGFR transactivation in response to some active substances such as Ang II [XREF_BIBR, XREF_BIBR], we examined the effect of KX2-391 on the phosphorylation of EGFR in the peritoneum after CG injury."
29137389
reach
"TGF-beta1-induced early Smad3 phosphorylation is independent of transient EGFR transactivation and ERK1/2 activation initiated by HB-EGF release, whereas Src mediated chronic EGFR transactivation and ERK1/2 activation participate in Smad3 activation in a relatively modest and delayed manner."
28943431
reach
"First, Src and Gbetagamma mediate the endocytosis of EGFR, which is required for proper EGFR signaling."
29885323
reach
"Since EGFR inhibition was effective on stiff but not on soft pillars, and EGFR activation through Src was force dependent, we hypothesized that Src dependent activation of EGFR was required for rigidity sensing."
28459445
reach
"C-Src modulates epidermal growth factor receptor (EGFR) activation and amplifies its downstream oncogenic signals."
32517369
reach
"One of the effects of Src overexpression is to enhance coupling of the EGF receptor to PI3K signalling [XREF_BIBR]."
11597319
reach
"Based on preclinical studies, other strategies to augment EGFR inhibition includes use of bortezomib in combination with EGFR kinase inhibitors due to its growth inhibitory and pro apoptic effects on cancer cell lines [XREF_BIBR] and dasatinib in combination with EGFR kinase inhibitor as in vitro data from NSCLC cell lines demonstrates that Src inhibition may enhance the antitumor activity of EGFR inhibition in the presence of EGFR mutations [XREF_BIBR]."
23800712
reach
"Moreover, enormous reports indicate that Src protein play a crucial role in EGFR transactivation [XREF_BIBR, XREF_BIBR] and other study shows that integrin beta3 elicits Src mediated EGFR transactivation [XREF_BIBR]."
25738362
reach
"These findings indicate that, in our MPS IIIB cell model, c-Src phosphorylation might mediate EGFR activation with subsequent signaling leading to the hypertrophic phenotype."
29348482
sparser
"GPER1 and Src controlled Ishikawa cell carcinogenesis in different manners: GPER1 accelerated EGFR mobility without affecting ERα activity, while Src activated ERα and EGFR without any change in GPER1 expression."
37257767
reach
"Src, as a mediator of receptor transactivation, can uniquely activate EGFR in the absence of EGFR ligand, and a Src inhibitor is synergistic with an EGFR monoclonal antibody in vitro in eliciting growth inhibition."
35059624
reach
"Several studies have shown that the Src mediated activation of EGFR plays critical roles not only in cell proliferation but also in the initiation and progression of vascular injury such as atherosclerosis."
25505586
reach
"In this context, it has been reported that Src mediated EGFR transactivation is required for Ang II induced production of TGF-beta1, 36 and sustained EGFR activation can induce arrest of epithelial cells at the G2/M phase, by which they acquire a prominent profibrotic phenotype and produce profibrotic growth factors and cytokines such as TGF-beta1."
26444028
reach
"We conclude that PAR (2)-triggered PGE (2) formation in A549 cells involves a coordinated up-regulation of COX-2 and mPGES-1 involving cPLA (2), increased cytosolic Ca (2+), PKC, Src, MEK-ERK, p38 MAPK, Src mediated EGF receptor trans-activation, and also metabolic products of both COX-1 and COX-2."
16120814
reach
"Collectively, these results indicated that Src mediates activation of EGFR, which in turn, activates the PI3K and AKT and ERK signaling pathways in cultured mouse RPTC."
21780115
reach
"Thus, the Dsg2 dependent EGFR activation may be modulated, in part, by c-Src."
26918609
reach
"It is not known, however, whether this is an autophosphorylation event or other tyrosine kinases, such as Src, which is known to activate EGFR, are responsible."
14729174
reach
"In addition, Src dependent activation of EGFR under oxidative stress has been reported to occur in a ligand independent manner and can not be blocked by inhibitors against EGFR kinase activity."
24399295
signor
"The c-terminal autophosphorylation domain of egfr was extensively phosphorylated by c-src./These studies revealed that y1086 was phosphorylated to a significantly higher extent by c-src than by egfr. Additionally, y1101 was identified as a unique c-src phosphorylation site"
8845374
reach
"Therefore, it appears that a PAR-stimulated activation of Src leads via an intracellular route to a ligand-independent phosphorylation-dependent activation of the EGFR."
24215724
reach
"At the mechanistic level, we prove that the induction of PGE2 and VEGF by ET-1 involves Src mediated epidermal growth factor receptor transactivation."
15347673
reach
"On the other hand, Src can also indirectly activate EGFR through promoting release of soluble forms of EGFR ligands via a mechanism involved in the activation of matrix metalloproteinases [XREF_BIBR]."
29137389
reach
"In addition, beta-arrestin has been shown to recruit Src to some GPCRs and the association of EP4, beta, arrestin1, and Src complex has been shown to induce the activation of EGFR and Akt."
26535079
reach
"These results suggested that Src, Gbetagamma, and EGFR endocytosis are involved in the GRK2 mediated inhibitory effects of EGFR on D 3 R signaling.Tyrosine phosphorylation of GRK2 is involved in EGFR [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
29885323
sparser
"Next to this so-called canonical AHR signaling pathway, the dissociation of the multiprotein complex leads to the release of c-Src, which subsequently may activate the epidermal growth factor receptor (EGFR) and downstream mitogen-activated protein kinase signal transduction ( xref – xref ) ( xref )."
35311158
reach
"In our short-term (1 h) experiments, autonomous Src activation actually slowed-down 125 I-EGF internalization (thus presumably EGFR internalization) yet increased EGFR intracellular pool, pointing to [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
20832399
reach
"In support of this, inhibition of Src kinase activity by PP1 or siRNA blocked PAR-2-induced EGFR signaling cascade and cell growth."
16816379
reach
"For example, we show that PI3Kgamma phosphorylates Src, which mediates EGFR transactivation."
27169346
reach
"Furthermore, Src family kinases has been suggested to increase the EGFR Y845 levels in cetuximab resistant clones derived from lung NCI-H226 cells [XREF_BIBR] and also implicated in erlotinib resistance in head and neck cancer [XREF_BIBR]."
27716204
sparser
"EGFR can also be activated in a ligand-independent manner by cellular Src (c-Src), a non-receptor tyrosine kinase."
22834827
reach
"Therefore, it is likely that the activation of Src by OVA induces the transactivation of EGFR via pro-HB-EGF shedding and the direct phosphorylation of EGFR at Tyr 845, both of which activate EGFR, resulting in the activation of Rho-kinase in VSMCs through unidentified pathway."
25505586
reach
"XREF_BIBR - XREF_BIBR Src may enable EGFR to evade degradation by promoting the destruction of Cbl, a kinase responsible for the ubiquitination and degradation of multiple receptors, including EGFR."
20378502
reach
"Similarly, our results indicated that PTHrP (1–34)-induced ERK1/2 and Akt activation require prior PI3K activation, which is dependent on ROS production and subsequent Src-mediated EGFR activation."
30926678
reach
"Downregulation of PTPRO in CRC cells caused SRC activation and subsequent EGFR and c-CBL ubiquitin ligase phosphorylation, both promoting EGFR stability (Asbagh et al., 2014)."
29031806
reach
"The increase in phosphorylation level of Src is earlier than that of EGFR phosphorylation, indicating that Src kinase might mediate EGFR transactivation in MCs."
30926678
signor
"The c-terminal autophosphorylation domain of egfr was extensively phosphorylated by c-src./These studies revealed that y1086 was phosphorylated to a significantly higher extent by c-src than by egfr. Additionally, y1101 was identified as a unique c-src phosphorylation site"
8845374
reach
"This suggests that Src mediates EGF receptor (EGFR)-dependent regulation of the Hippo pathway, even though we previously reported that the Src inhibitor PP2 did not block the effect of EGF on YAP."
26216901
reach
"subsequently, Src promotes the shedding of heparin binding EGF like growth factor and therefore EGFR activation [XREF_BIBR], which in turn activates several signaling cascades, such as the ERK, PI3 kinase and phospholipase C pathways [XREF_BIBR, XREF_BIBR]."
24304271
reach
"Src phosphorylates EGFR in C-terminal (Y1101) and catalytic domains (Y845), and phosphorylation of Y845 by Src promotes EGFR mediated DNA synthesis [XREF_BIBR]."
19275932
reach
"In particular, Src, as a mediator of receptor transactivation, can uniquely activate EGFR in the absence of EGFR ligand, and a Src inhibitor is synergistic with an EGFR monoclonal antibody in vitro in eliciting growth inhibition."
19360146
reach
"Independent from the previously discussed FAK Tyr397 notion, a direct EGF effect as suggested by Yamanaka and co-workers with the inclusion of a Src mediated EGFR transactivation may also become plaus[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
26079101
reach
"Moreover, pharmacological inhibition of Src and EGFR blocked Alp- and Car stimulated EGFR transactivation."
18787115
reach
"Inhibition of Src kinase activity and ROS may inhibit the EGFR activation."
20123015
reach
"Given that activation of alpha 1 -AR induces Src-Stat3 binding and that Stat3 is a downstream target of EGFR, it is possible that Src may serve as EGFR downstream effector to mediate hepatic cell function, although the possibility of Src induced EGFR activation can not be excluded."
18314882
reach
"These data indicate that c-Src function as an upstream signaler to mediate EGFR transactivation by LPS, which is consistent with these studies that Ang II and TGF-beta activated EGFR signaling pathway via c-Src [XREF_BIBR, XREF_BIBR]."
29207668
reach
"These results together suggested that TLR4 and c-Src signaling mediated PA triggered EGFR activation."
27087279
reach
"In contrast, inhibition of Src with PP1 blocked EGF receptor activation and RPTC proliferation after oxidant injury."
18171996
reach
"In the absence of ligand, EGFR or HER2 could be activated by Src 25."
28459445
reach
"Several observations suggest that the interaction between TACE and Src is of physiological significance and activated forms of Src can stimulate the EGFR and ERK signaling by activation of TACE and release of EGFR ligands."
24520077
reach
"The activation of Src depends on FAK, and then causes the transactivation of EGFR."
33193253
sparser
"These data suggest that Src activates EGFR through the interaction of both Src-EGFR and Src-caveolin-1, and then antagonizes TRAIL-induced apoptosis in gastric cancer cells."
24840271
sparser
"In line with these findings, Src-kinase can directly activate the EGFR kinase and consequently activate ERK1/2 in Müller cells ( xref )."
27930693
reach
"These results indicate that IL-17A-induced Src activation and Src mediated transactivation of EGFR are required for Lrig1 + stem cell expansion and migration in response to IL-17A stimulation."
30578323
sparser
"In this system, DUOX-dependent H 2 O 2 activates Src kinase, which in turn activates EGFR in a ligand-independent manner."
24455491
reach
"Pretreatment with Src or Src family kinase inhibitors (PP2 and herbimycin A) abolished ouabain induced Src activation and formation of the active Na/K, ATPase, Src, and EGFR complex."
20144708
sparser
"UVB-induced AhR activation upregulates suppression of reversible tumor promotion before tumor the RAF-MEK1/2-ERK1/2 signaling pathway via c-Src-dependent EGFR activation, and when AhR is activated, it upregulates its specific target gene, cyp1a1 [ xref ]."
29285309
reach
"We further show that EGFR and HER2 are activated through phosphorylation by Src family kinases (SFK)."
28459445
reach
"Upon translocation into the nucleus, PKM2 is dephosphorylated at Ser37 through interaction with phosphorylated phosphatase Cdc25A at Tyr59, mediated by c-Src upon EGFR activation [XREF_BIBR]."
33292198
sparser
"ATP-mediated EGFR transactivation in airway epithelial cells was found to involve purinergic P2Y 2 receptor stimulation, and both ligand-dependent mechanisms as well as ligand-independent EGFR activation by the non-receptor tyrosine kinase Src."
23349873
sparser
"This may suggest that Src phosphorylates and activates the EGFR ( xref ), leading to the disruption of AJ ( xref )."
32038981
reach
"SRC activation, which was also a prognostically significant finding in our previous study, induces CBL destruction and enables EGFR to evade destruction."
25348515
reach
"Our results show that overexpression of c-Src causes no change in EGFR half-life but does produce an increase in the internalization rate constant of EGF.EGFR complexes when the endocytic apparatus is not stoichiometrically saturated; this effect of c-Src on EGFR endocytosis is negligible at high receptor occupancy in cells overexpressing the receptor."
9374500
reach
"To our knowledge, this is the first report to demonstrate the combined inhibition of both PLCgamma-1 and c-Src abrogates EGFR mediated tumor cell invasion."
18594017
sparser
"C-Src activates EGFR by phosphorylation on residue Tyr845 xref that is located in the activation loop of the catalytic domain."
21152443
sparser
"Gao and colleagues [28] demonstrated that I-BOP induces Src kinase activation and phosphorylation of EGF receptor and extracellular-signal-regulated kinase 1/2 (ERK 1/2) in a bladder cancer cell lin[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
15519496
trips
"These data suggest that Src activates EGFR through the interaction of both Src-EGFR and Src-caveolin-1, and then antagonizes TRAIL-induced apoptosis in gastric cancer cells."
24840271
reach
"Third, Src mediates EGFR transactivation."
26444028
reach
"SRC and ADAMs signaling mediates PGE 2 -induced release of EGFR ligands."
28415726
reach
"Thus, Src activated EGFR colocalized with integrin clusters at peripheral adhesions only when they were under force."
28459445
sparser
"In addition, Src-dependent activation of EGFR under oxidative stress has been reported to occur in a ligand-independent manner and cannot be blocked by inhibitors against EGFR kinase activity."
24399295
reach
"The transcription factor Stat5 is activated by phosphorylation after docking to EGFR or indirectly through Src mediated EGFR signaling [XREF_BIBR, XREF_BIBR]."
20459599
sparser
"Overall, these findings, together with c-Src-dependent EGFR transactivation, suggest that NAGLU-deficient cardiomyoblasts develop a hypertrophic phenotype through a coordinated intracellular and extracellular EGFR activation induced by c-Src and HB-EGF, respectively."
29348482
reach
"Src tyrosine kinase inhibitor PP2 suppresses ERK1/2 activation and epidermal growth factor receptor transactivation by X irradiation."
16414009
reach
"However, TGF-beta1-induced Src activation, delayed EGFR phosphorylation at Y845 and subsequent ERK1/2 activation may modulate Smad2/3 phosphorylation and downstream fibronectin accumulation.The presen[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
28943431
reach
"To further test whether Src caused a redistribution of unaltered total EGFR away from the surface-accessible pool, competent for ligand binding, cells were surface labeled at 4 degreesC for 2 h with E[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
20832399
reach
"STATs can be activated by interacting directly with EGFR through SH2 domains or indirectly through Src mediated EGFR signaling [XREF_BIBR]."
18778701
reach
"In some cases of NSCLC expressing mutant EGFR, gefitinib does not inhibit cell proliferation, but PP2 does, collectively suggesting that gefitinib resistance of the mutant EGFR is due to the Src dependent modulation of EGFR activity."
23702846
reach
"It has been demonstrated that c-Src, which is nontransforming when overexpressed alone, can potentiate the tumorigenic capacity of overexpressed HER1."
11250711
reach
"Radiation activated Src kinase initiates EGFR internalization and nuclear transport."
22666662
reach
"Our results show that the activation of the EGFR increases trans-phosphorylation of integrin beta3 allowing the recruitment of Src, which activates both the EGFR and integrin beta3, amplifying the signaling cascade leading to the activation of downstream targets regulating migration."
22227249
reach
"Overexpression of c-Src promoted internalization of the EGFR [3]."
14644164
reach
"Target Modulation by a Kinase Inhibitor Engineered to Induce a Tandem Blockade of the Epidermal Growth Factor Receptor (EGFR) and c-Src : The Concept of Type III Combi Targeting."
25658745
reach
"On the other hand, our study showed that inhibition of TGF-beta1-mediated HB-EGF or Src activity prevents EGFR transactivation and ERK1/2 activation, consequently inhibiting fibronectin upregulation."
28943431
reach
"We have previously demonstrated that both PLCgamma-1 and c-Src mediate HNSCC invasion downstream of EGFR (Thomas 2003, Zhang 2004)."
20622897
reach
"A Src specific inhibitor, PP2 suppressed activation of Src, EGFR, Caveolin-1, PDK1, Akt, DNA-PKcs, and ATM under severe hypoxia (Figs. 3A and 4)."
30224064
reach
"However, Gβγ released during activation of CRF R by CRF, particularly from G , stimulates phosphorylation of Src and PYK2, which in turn promotes transactivation of the EGFR through the formation of a heterotrimeric complex formed by the association of CRF R, Src, and EGFR."
31920979
sparser
"This scenario would still allow a rapid AHR- and c-Src-dependent endogenous activation of EGFR (Y845) and downstream signal transduction by DLCs, but would exclude an activation of the RTK through auto-/paracrine events."
34991250
reach
"In the same cell line, however, the Src kinase inhibitor PP1 only slightly reduced LPA induced EGFR transactivation [XREF_BIBR *], and recent data [XREF_BIBR] suggest Src as a point of convergence downstream of RTK transactivation and G-protein-mediated focal adhesion complex assembly."
11250708
sparser
"In conclusion, the c-Src-dependent EGFR activation may play an important role in Ang II-induced cardiac hypertrophy, and inhibition of EGFR by specific molecules may be an effective strategy for the treatment of Ang II-associated cardiac diseases."
26762600
reach
"SRC family kinases are activated in non small cell lung cancer and promote the survival of epidermal growth factor receptor dependent cell lines."
17200208
reach
"These results suggest the involvement of a Src family kinase in the PAF induced transactivation of EGFR in SKOV-3 cells."
25261977
reach
"In PLC/PRF/6 cell line, complete inhibition of activated Src by dasatinib at the dosage of 0.1 uM, not only induced the inhibition of Akt activity at the same dosage, but also induced the inhibition of p-EGFR at Tyr1068 at higher dosage of 10uM."
23721490
reach
"Indeed, in murine fibroblasts, overexpression of c-Src has been shown to potentiate the mitogenic and tumorigenic capacity of the overexpressed EGFR."
9990038
reach
"To date, G s -, cAMP-, PKA- and ADAM-17-dependent production of EGF like factors and consequent activation of the EGFR/MAPK3/1 pathway have been clearly elucidated in mammalian preovulatory follicles, but an alternative PKA independent pathway involving Src kinase mediated activation of the EGFR has also been described."
26688146
reach
"Src kinase activation following irradiation triggered caveolin-1 dependent EGFR internalization into caveolae."
18789131
reach
"Our and other groups have reported that Src family kinases (SFKs) can mediate EGFR activation in response to different stimuli including oxidant injury."
21780115
reach
"Taken together, these observations would suggest that primary Src activation may be sufficient to promote EGFR signalling and internalization."
20832399
sparser
"When AKAP121 is transfected, Src-dependent activation of the EGF receptor is diminished because PTPD1 is recruited to mitochondria [ xref ]."
21355846
reach
"These results provided evidence that guggulsterone induced ERK1/2 phosphorylation through Src mediated activation of EGFR."
23119029
reach
"There are several different mechanisms by which STAT proteins can mediate intracellular EGFR signaling, including direct activation of STATs by EGFR binding and indirect activation of STATs through Src mediated EGFR signaling."
17661350
reach
"This suggests that EGFR activation was mediated by Src-mediated transactivation (25), since AZD0530 is a relatively weak direct inhibitor of EGFR (47)."
34088769
sparser
"Accumulating evidence has shown that EGFR is a downstream signaling molecule of c-Src and c-Src could directly bind with EGFR and activate EGFR [ xref , xref , xref ]."
25958313
reach
"ROS derived NADPH oxidase activation by tobacco smoke induces metalloproteinase TACE activation in a Src and PKCepsilon dependent manner, which induces the processing and release of amphiregulin and EGFR activation [XREF_BIBR]."
23434665
reach
"In that study, Src activation by hydrogen peroxide induced EGFR transactivation without phosphorylation of Tyr1173, an autophosphorylation site of the activated EGFR [20]."
16414009
reach
"These data suggest that ouabain dephosphorylates cofilin through Src mediated activation of EGFR and that EGFR activation is under the control of Src mediated inter cross-talk between Na,K-ATPase and [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
16713181
reach
"Previously, we showed that Src mediated EGF receptor transactivation and ERK activation mediates ammonia induced astrocyte swelling, which represents a major component of brain edema in hyperammonemic disorders."
32125625
reach
"Src increases EGFR mediated pathway activity in many cancer types and can be activated via FAK binding which initiates a crosstalk between integrin-FAK signaling and other pathways involved in glioma invasion [XREF_BIBR, XREF_BIBR, XREF_BIBR]."
28629170
reach
"Further, SRC upregulation was shown to mediate EGFR activation in GC cells through the RANKL/RANK pathway, thus abrogating sensitivity to the EGFR inhibitor cetuximab."
32082487
reach
"Dittmann et al. reported that Src kinase activation following irradiation triggers Cav-1 dependent EGFR internalization into caveolae."
25788263
sparser
"The Src/EgfR module includes Src-dependent activation of EgfR; if either component is missing from the initial state, signaling along this cascade is compromised."
19317917
reach
"It has been proposed that phospho-Tyr845 and its surrounding amino acid sequence provide a docking site for the SH2 domain of Src enabling formation of EGFR/Src physical complexes."
35083168
reach
"Arsenic can stimulate c-Src activity, which can then activate EGFR by physical interaction resulting in two unique tyrosine phosphorylation events (Tyr845, Tyr1101), leading to ligand independent EGFR phosphorylation and constitutive activation [XREF_BIBR - XREF_BIBR]."
23510327
sparser
"Oxidised Src then promotes ligand-independent phosphorylation and activation of EGFR."
21975295
sparser
"Src can activate EGFR either directly through the phosphorylation of EGFR at Tyr-845 in the cytoplasm (Sato et al. xref ; Biscardi et al. xref ), or indirectly via the metalloproteinase-catalyzed release of HB-EGF from pro-HB-EGF (Pai et al. xref )."
25505586
reach
"Based on these findings, PAR 4 -mediated EMT is considered to be produced through Src mediated EGFR activation."
17433115
reach
"With the limitations of analyzed responses, EGFR signalling phosphorylation in MDCK cells upon either short-term Src activation or low EGF exposure mainly occurred at or very close to the cell surface[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
20832399
reach
"Src family kinases mediate epidermal growth factor receptor signaling from lipid rafts in breast cancer cells."
21775822
reach
"Dasatinib, a dual SRC and ABL inhibitor that also targets EGFR and KIT, elicits anti-tumorigenic effects in preclinical studies [XREF_BIBR, XREF_BIBR]."
27732969
reach
"In contrast, Akt activation via CRF 1 R is mediated by the Src/PI3K pathway with little contribution of EGFR transactivation."
31920979
reach
"In colon cancer, loss of Dsg2 leads to a compensatory increase in Dsc2 expression and the increased Dsc2 suppresses cell proliferation by inhibition of EGFR downstream signaling such as Src [XREF_BIBR]."
32989241
signor
"Revealed that peptides derived from egfr residues y992, y1086, y1101, and y1148 bound directly to the sh2 domain of c-src (figure 8c). These experiments demonstrate that a specific subset of egfr receptor c-src phosphorylation sites are also ligands for the sh2 domain of c-src.Cellular src functions as a co-transducer of transmembrane signals emanating from a variety of growth factor receptors, including egfr"
8845374
reach
"This might explain previous results showing that Erk1/2 activation induced by antibody cross linking of PrP is mediated by EGFR signaling and that Src kinase activity increases EGFR endocytosis during EGF stimulation."
22438585
reach
"Spatial EGFR Dynamics and Metastatic Phenotypes Modulated by Upregulated EphB2 and Src Pathways in Advanced Prostate Cancer."
31805710
reach
"Transcriptional upregulation of egfr by Src overexpression was confirmed through qRT-PCR from whole midguts (Fig XREF_FIG H)."
24788409
sparser
"In summary, the present study provides novel findings that the downstream signaling from Src-activated EGFR links to Rho-kinase-mediated MLCP inactivation, thereby regulating smooth muscle contractility."
25505586
reach
"PTHrP (1–34) exposure induced reactive oxygen species (ROS)-dependent, Src kinase-mediated epidermal growth factor receptor (EGFR) transactivation and subsequent Akt and ERK1/2 activation, which involve in fibronectin up-regulation."
30926678
sparser
"This therefore suggests that in this system the EGF receptor and perhaps not Src activation may be coupled to this pathway [73] ."
9920408
sparser
"We conclude that ME-induced cardioprotection is mediated via Src-dependent EGFR transactivation and activation of the PI3K and MAPK pathways."
15563540
reach
"35 In H2228 cells, Src inhibitors alone or in combination with ALKi increased the percentage of apoptotic cells similarly to ALK and gefitinib, suggesting that Src mediates ALK and EGFR signaling in NSCLC."
23567620
reach
"Thus, in the absence of added ligand, Src activation was able to induce intracellular sequestration of EGFR and this effect was specific since the sizeable fraction of intracellular TfR at 40 degreesC[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
20832399
sparser
"Given that activation of α 1 -AR induces Src-Stat3 binding and that Stat3 is a downstream target of EGFR, it is possible that Src may serve as EGFR downstream effector to mediate hepatic cell function, although the possibility of Src-induced EGFR activation cannot be excluded."
18314882
reach
"Ang-(1-7)/ MAS1 receptor axis inhibits allergic airway inflammation via blockade of Src-mediated EGFR transactivation in a murine model of asthma."
31675376
reach
"In summary, the present study provides novel findings that the downstream signaling from Src activated EGFR links to Rho-kinase-mediated MLCP inactivation, thereby regulating smooth muscle contractility."
25505586
reach
"It has also been reported that individually or combined inhibition of PLC-gamma and c-Src could block EGFR mediated HNSCC cell invasion."
26291058
reach
"Speculatively, upregulation of GRP induced Src signalling could enhance EGFR signalling in Basal_3 tumours independently of ADAM17, which can be repressed locally by stroma secreted ADAM17 inhibitors."
24901235
reach
"mTOR Inhibition Leads to Src-Mediated EGFR Internalisation and Degradation in Glioma Cells."
32823532
reach
"In NSCLC, EGFR transactivation is also mediated by ROS dependent NADPH oxidase activity and c-Src, which results in the downstream activation of the PI3K/AKT/NF-kappaB pathway and cyclooxygenase-2, which are molecular predictors of the overall survival of patients with NSCLC [XREF_BIBR]."
23434665
reach
"ADAM10 is activated downstream of Src thereby modulating EGFR activation via release of EGF and Betacellulin (BTC)."
34434944
reach
"Interestingly, Dittmann et al. showed that Src kinase activation following irradiation triggers Cav1 dependent EGFR internalization into caveolae [XREF_BIBR]."
23521716
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"Activation of PKC-alpha provokes cooperative signaling that results from Src dependent activation of the EGFR/ERK1/2 pathway and EGFR independent activation of p38-alpha."
28008134
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"Although these authors used the compounds at a high concentration (50 μM), the results suggest a possibility that GPER/GLP-1R-NOX1-nSMase2-ceramide-KSR1 signaling is necessary for Ras-PI3K/ERK signaling downstream of Src-activated EGFR in C6 cells ( xref C)."
30889865
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"Moreover, Src family kinases, which are frequently activated in HNSCC, can promote EGFR independent STAT3 activation XREF_BIBR."
22257382
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"Our results indicate that the late phase of Smad3 phosphorylation is partly dependent on delayed EGFR transactivation mediated by Src kinase."
28943431
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"XREF_BIBR, XREF_BIBR Src can also induce activation of EGFR through direct phosphorylation at Tyr845."
26444028
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"In this system, DUOX dependent H 2 O 2 activates Src kinase, which in turn activates EGFR in a ligand independent manner."
24455491
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"Put together, these data suggested that early Smad3 phosphorylation is independent of transient EGFR transactivation and ERK1/2 activation initiated by HB-EGF release, whereas the late phase of Smad3 [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
28943431
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"The CXCL12 induced migration was inhibited by the SRC family kinase inhibitor PP2 (10 microM; XREF_FIG), as was the activation of EGFR, ERK and Akt pathways (XREF_FIG)."
28781651
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"Through its kinase activity, Src potentiates the effects of EGFR activation [XREF_BIBR, XREF_BIBR, XREF_BIBR]."
33450835
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"In our previous study, we demonstrated that Src dependent activation of EGFR was required in the sensitization process."
15911880
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"In contrast, TNF-alpha-induced NFkappaB activation was not prevented by EGFR or Src inhibition, suggesting that TNF-alpha exerts both EGFR dependent and -independent effects."
21212278
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"Some studies reported that AKI induced fibrosis is mediated by ligand independent activation of EGFR by SRC kinase at Y845 and might involve production of ROS."
27642633
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"Ligand Independent EGFR Activation by Anchorage Stimulated Src Promotes Cancer Cell Proliferation and Cetuximab Resistance via ErbB3 Phosphorylation."
31615015
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"In a further attempt we investigated whether the above mentioned pathways can be bypassed by GPCR induced Src activation of EGFR."
26921391
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"The interactions between EGFR and c-Src are bi-directional, in the sense that c-Src can bind, phosphorylate and activate EGFR and vice versa."
29348482
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"In contrast, EGFRvIII + tumors were driven by activation of the prototypical Src family kinase c-Src that promoted VEGF secretion leading to angiogenic tumor growth."
27286795
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"Two pathways of LPA mediated transactivation of EGF-R have been described : the first involves activation of matrix metalloproteinases (MMPs), cleavage of pro-HB-EGF, and subsequent ligation and activation of EGF-R [XREF_BIBR, XREF_BIBR, XREF_BIBR, XREF_BIBR], and the second pathway is HB-EGF shedding independent involving the intracellular activation of EGF-R by Src kinases [XREF_BIBR, XREF_BIBR]."
18996473
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"Thus, we tested whether TLR4 and c-Src mediates ox-LDL-induced EGFR activation in macrophages."
28374780
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"The protein kinase activity of PI3K phosphorylates serine residue 70 on Src to enhance its activity and induce EGFR transactivation following betaAR stimulation."
27169346
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"EGFR dependent STAT activation may be mediated by Src without JAK."
24381541
sparser
"Transactivation of EGFR by angiotensin II (AngII), ET-1, or bradykinin involves ROS-dependent activation of c-Src, which then activates EGFR and leads to ERK activation and pro-growth signaling [ xref – xref ]."
24132149
sparser
"The effects of Cd on cell proliferation are mainly through GPER activation and phosphorylation of Src, which then activates MMPs, and they in turn cleave pro-HB-EGF into HB-EGF to activate EGFR; phosphorylated Src can also directly activate EGFR initiating downstream MAPK signaling ( xref )."
31468104
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"Similarly, Src activated Epidermal Growth Factor Receptor (EGFR) signals through Ras-MAPK to engender phosphorylation of the E-box binding transcription factor USF and facilitate its interaction with activated Smad2/3 to regulate PAI-1 gene expression [XREF_BIBR]."
22204556
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"Since STAT activation mediates EGFR and Src synergism and Akt and Erk can also be activated by Src, these findings suggest that mutant EGFRs induce a constitutive activation of the Src signaling pathway."
19305428
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"These results provide evidence that in human colon cancer cells guggulsterone stimulates cell proliferation through Src mediated activation of EGFR and ERK1/2."
23119029
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"Previous studies have linked GPR30 expression to the non receptor tyrosine kinase (Src)-dependent activation of EGFR signaling in a variety of estrogen responsive cancer cells [XREF_BIBR]."
29096683
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"Src kinases mediate EGFR transactivation of Trk receptors."
23416450
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"Surprisingly, even in the absence of EGF addition, c-Src expression induced activation of EGFR and of EGFR mediated downstream signaling targets ERK and Shc."
18448311
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"Src directly modulates EGFR function through phosphorylation of tyrosine residues on EGFR that allows for coupling to downstream signaling events."
21266529
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"Combined inhibition of PLCgamma-1 and c-Src abrogates Epidermal Growth Factor Receptor mediated head and neck squamous cell carcinoma invasion."
18594017
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"Src can also directly activate EGFR by causing Y845 phosphorylation of EGFR and recruitment of alternate signaling molecules xref , xref ."
30679495
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"In addition, PGE 2 -induced EP4 receptor signaling induces MMP production and ovarian cancer cell invasion through Src mediated EGFR transactivation [XREF_BIBR]."
32363546
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"In this situation c-Src leads to EGFR activation through the phosphorylation of unspecified tyrosine residues [XREF_BIBR]."
27086143
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"Src signaling induced by T. gondii triggers trans-activation of EGFR that is required to prevent parasite killing within host cells."
29036202
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"Since Abl2 rather than Src, a regulator of membrane ruffling during macropinocytosis, mediated downstream signaling of EGFR, we propose that the selective effector targeting downstream of EGFR determines whether HPV16 endocytosis or macropinocytosis is induced."
32188731
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"PLSCR1 activity affects EGFR related signaling and its downstream effectors, including the adaptor protein Shc, Src, and Erk kinases in fibroblasts and epithelial cells [XREF_BIBR]."
23259795
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"One possible explanation is that, although the pathway mapping using RPMA produces a multiplexed view of cell signaling, the pathway signature in this study did not include every single known protein [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
19881954
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"Src and Pyk2 mediate G-protein-coupled receptor activation of epidermal growth factor receptor (EGFR) but are not required for coupling to the mitogen activated protein (MAP) kinase signaling cascade."
11274221
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"To assess the role of Src-dependent EGFR activation in the onset of lapatinib resistance, we transfected the sensitive MDA-MB-361 cell line with either the wild-type EGFR or the mutant Tyr845Phe (Y845F) variant of EGFR."
24887236
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"The second most commonly elevated pathway was epidermal growth factor receptor signaling (24 of 31 tumor types), led by canonical oncogenes EGFR and SRC."
35380699
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"These pathways are initiated by the interaction of CGs to Na /K -ATPase to activate Src tyrosine kinase, which in turn activates the epidermal growth factor receptor (EGFR)."
29117117