IndraLab
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"As shown in Figure 2B‐E, individual treatments of erlotinib, AG490, LY294002 and PD98059 all led to a substantial decrease in YD‐38 cell survival.3.3
Knockdown of Src causes a strong inhibition of the phosphorylation of EGFR, STAT-5, PKB and ERK-1/2 in YD-38 human oral cancer cells."
rlimsp
"In this regard, our observation that another electrophilic insult, Zn2+, can induce Src-dependent EGFR transphosphorylation (Wu et al. 2002) is consistent with our previous report of Zn2+-induced inhibition of PTPs (Tal et al. 2006), and may reflect a uniform mechanism to oxidant stress that is also relevant to other environmental electrophiles."
sparser
"Another point of interest is the fact that the two partners in the well-known bidirectional activatory trans-phosphorylation between EGFR and Src, where Src phosphorylates the EGFR [ xref – xref ], and the EGFR phosphorylates Src [ xref ], are regulated by CaM, albeit in different manners."
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"Activation of Src kinase triggers Src dependent phosphorylation of epidermal growth factor receptor and an activation of Ras and MAPK (mitogen activated protein kinase) cascade as well as numerous other signaling pathways important for vascular smooth muscle function and phenotype."
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"Indeed, the transfection of H9C2 sh-CTR and H9C2 sh-NAGLU clones with a dominant negative (DN) c-Src, while had no effects on H9C2 sh-CTR clones, caused the reduction of EGFR phosphorylation in the H9C2 sh-NAGLU as detected by western blotting analysis, indicating that EGFR phosphorylation in our cellular model of MPS IIIB might be mediated also by c-Src."
sparser
"Moreover, hydrogen peroxide strongly activated the EGFR, a process that was inhibited by the Src inhibitor PP1 ( not shown ), suggesting that this was a consequence of EGFR phosphorylation by Src, as this process has been extensively documented [ xref – xref ], and it is known that H 2 O 2 induces EGFR transactivation by a Src-mediated mechanism [ xref ]."
sparser
"Recent work has also highlighted a co-localization between Src with EGFR, particularly within lipid rafts of cancer cells [ xref ], Moreover, it was reported that Src could phosphorylate EGFR [ xref , xref ], and mediate EGFR signaling in various cancer cell lines [ xref , xref ]."
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"Recent work has also highlighted a co-localization between Src with EGFR, particularly within lipid rafts of cancer cells [XREF_BIBR], Moreover, it was reported that Src could phosphorylate EGFR [XREF_BIBR, XREF_BIBR], and mediate EGFR signaling in various cancer cell lines [XREF_BIBR, XREF_BIBR]."
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"Moreover, Ang II activated EGFR signalling in renal proximal tubule epithelial cells results mostly by the non-ligand-mediated receptor transactivation mediated by ROS-dependant Src activation, which leads to phosphorylation of both EGFR and Caveolin-1 and their association in the lipid rafts (XREF_FIG)."
rlimsp
"Moreover, hydrogen peroxide strongly activated the EGFR, a process that was inhibited by the Src inhibitor PP1 (not shown), suggesting that this was a consequence of EGFR phosphorylation by Src, as this process has been extensively documented [35–39], and it is known that H2O2 induces EGFR transactivation by a Src-mediated mechanism [40]."
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"We are the first to report an increase in SRC activity with mTORC1 inhibitor treatment and intriguingly SRC phosphorylates and transactivates EGFR, raising the question of whether SRC activation may itself provide a potential mechanism for increased EGFR phosphorylation in the setting of mTORC1 inhibition."
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"In quiescent HSCs, CD95L led to a rapid phosphorylation of the epidermal growth factor receptor (EGFR), extracellular signal regulated kinase (Erk), and c-Src, but not of c-Jun-N-terminal kinase and p47 (phox), an activating subunit of reduced nicotinamide adenine dinucleotide phosphate oxidase."
sparser
"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 ]; SRC also enhances EGFR activation of the JAK-STAT pathway [ xref ] (see Weimbs review)."
reach
"Another point of interest is the fact that the two partners in the well-known bidirectional activatory trans-phosphorylation between EGFR and Src, where Src phosphorylates the EGFR [XREF_BIBR - XREF_BIBR], and the EGFR phosphorylates Src [XREF_BIBR], are regulated by CaM, albeit in different manners."
rlimsp
"Collectively, the analyses of cells expressing Y845F mutations or DN-Src provide strong support for the conclusion that constitutive activation of mutant EGFRs is transduced into oncogenic signaling through cooperative signaling with Src and involves obligatory role of the major Src phosphorylation site on EGFR."
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"We thus took advantage of specific Src kinase activity inhibitor PP1 and SU6656 to investigate the effects of Src kinase on EGFR transactivation and subsequent Akt activation, and found that Src kinase inhibition blocked PTHrP (1–34)-induced EGFR and Akt phosphorylation (Figure 2D)."
rlimsp
"Based on our results, we propose that this direct phosphorylation of the cytoplasmic tails of EGFR and HER2 by c-Src may overcome the effects of tyrosine kinase inhibitors or antibodies or molecules against extracellular domains [17], since c-Src may act independently of EGFR and HER2 tyrosine kinase activity."
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"The EGF tyrosine kinase inhibitor AG-1478, the Src kinase inhibitor herbimycin A or naloxone eliminated phosphorylation of EGF receptor and the cytoprotective effect.312 The aforementioned data indicate that there is an important role of transactivation of opioid and adenosine receptors in cardiac tolerance to the impact of ischemia and reperfusion."
sparser
"It is interesting that anti-HGF monotherapy reduced EGFRvIII tyr 845 phosphorylation by ~50% suggesting receptor crosstalk either by direct receptor interactions or via indirect mechanisms such as src-dependent EGFR phosphorylation as observed by Tice et al. in wild-type EGFR ( xref , xref )."
rlimsp
"Mutation at tyrosine 869 (845) residue, an Src phosphorylation site, decreased the phosphorylation levels of wild-type EGFR and other mutants, but not that of S768I and L861Q mutants, suggesting that S768I and L861Q mutants became Src independent for their activation and biological functions."
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"Given that Src activity is involved in generating EGFR TKI resistance (XREF_FIG), it is possible that aberrant activation, and conformation of the EGFR under CS exposure may be caused by Src dependent phosphorylation of other EGFR tyrosines, which is currently being investigated in our laboratory."
sparser
"There are two major mechanisms of EGFR transactivation: (1) stimulation of metalloproteases which generate peptide EGFR ligands from their membrane-bound precursors, and (2) activation by reactive oxygen species of non-receptor tyrosine kinase Src, which phosphorylates intracellular domain of EGFR."
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"Src is known to be activated by C-terminally phosphorylated EGFR and capable of phosphorylating Y and therefore likely involved in this autocatalytic amplification on EGFR.Theoretically, the autocatalytic phosphorylation mechanism can generate only one collective state in which all receptors are fully active ."
rlimsp
"This defect in cell adhesion results from reggie effects on Src tyrosine kinases and epidermal growth factor receptor (EGFR): loss of reggies reduces Src activation and EGFR phosphorylation at residues targeted by Src and c-cbl and leads to increased surface exposure of EGFR by blocking its internalization."
sparser
"Furthermore, Csk-inactivated Src was activated by interaction with Src-phosphorylated EGF-R but not by autophosphorylated EGF-R. Upon EGF treatment of MCF7 or three colorectal carcinoma cell lines (WiDr, DLD-1, and LS174T), the EGF-R coimmunoprecipitated with both p85 alpha and Src."
rlimsp
"Importantly, a tyrosine to phenylalanine mutation of the major Src phosphorylation site on EGFR, Y845, reduced the constitutive phosphorylation of NSCLC-EGFR mutants, as well as that of STAT3, Akt, Erk and Src, and reduced the mutant EGFR-Src association as well as proliferation, migration and anchorage-independent growth."
reach
"Another potential mechanism by which H 2 O 2 may mediate EGFR transactivation is by oxidative activation of non receptor tyrosine kinases of the Src family XREF_BIBR, XREF_BIBR, which promote EGFR phosphorylation at selected residues in a ligand independent fashion XREF_BIBR, XREF_BIBR."
sparser
"Although overexpression or activation of Src does not significantly increase tumor cell proliferation, cotransfection of Src and EGFR leads to increased proliferation, invasiveness, and tumorigenesis in mice. xref , xref This appears to be accomplished in part by direct binding of Src to EGFR and phosphorylation of EGFR by Src. xref , xref This then leads to a conformational change in EGFR that promotes access to the ATP binding pocket of EGFR. xref This pathway allows EGFR TK to be activated in the absence of receptor ligand binding. xref , xref Although several receptors have been shown to play a role in EGFR transactivation, Src appears to be a common effector in this pathway."