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EGF activates ERK. 1000 / 2951
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"To test the hypothesis that MAPK activation could be dependent upon EGF-R transactivation, we also tested the effect of AG1478 on LTD 4 -induced ERK1/2 phosphorylation and found that 1 hour pretreatment with 250 nM of the EGF-R phosphorylation inhibitor totally prevented ERK1/2 activation by EGF and LTD 4 alone or by their combination (Fig. xref )."
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"In monolayer culture, expression of Gab2 at levels comparable with those detected in human breast cancer cells accelerated epidermal growth factor (EGF)-induced cell cycle progression and was associated with increased basal Stat5 tyrosine phosphorylation and enhanced and/or more sustained EGF induced Erk and Akt activation."
sparser
"Widely expressed with highest levels in bone marrow, spleen, brain, testes, and embryonic brain, Abi1 may negatively regulate cell growth and transformation by interacting with the nonreceptor tyrosine kinases ABL1 and/or ABL2, thus regulating EGF-induced Erk pathway activation and EGFR signaling."
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"It binds to Cat1 and Git1 through the Spa2-homology domain,24 and Cool-Cat1 and Git1 complexes are localized throughout the cytosol, along the cell membrane, and especially to focal adhesions, distinct structures that physically connect a cell to its extracellular environment (focal adhesions willbe discussed in more detail later).31 Because both Cooland Cat1 and Git1 can form homodimers, it is thought thatCool-Cat1 and Git1 complexes assemble into large oligo-meric complexes in cells as a mechanism to promote signal amplification.27,32,33 The localization of Cool-Cat1 and Git1 complexes to thecell surface has been shown to be important for mediat-ing G protein coupled receptor- and growth factorreceptor induced activation of Cdc42 and Rac, as well as for the regulation of Arf GTPase activation.27,31 Activa-tion of these signaling pathways lead to cytoskeletal rear-rangements which are required for promoting cancer cellmigration and invasion, and enhancement of cell growth.27,31 The ectopic expression of a mutant form ofCat1 and Git1 that is unable to associate with Cool abolishesthese effects, highlighting the importance of this proteinprotein interaction.34,35 The MEK1, ERK1/2, Cat1, and Git1 complex- Cat1 and Git1 hasalso been shown to promote the activation of the mitogen activated protein kinase ERK1/2.36 This is an out-come of a complex that can form at focal adhesions between Cat1 and Git1, MEK1.36 (i.e., the kinase that phosphorylates ERK1/2), and ERK1/2.37 Similar to Cool, MEK1 binds to the Spa-2 homology domain ofCat1 and Git1, an interaction that is enhanced when Cat1 and Git1 is phosphorylated by the non receptor tyrosine kinase c-Src.36,37 While it is not entirely clear how Cat1 and Git1 binds to ERK1/2, this interaction is augmentedfollowing the treatment of cells with epidermal growth factor (EGF).36 Interestingly, knocking-down Cat1 and Git1expression levels in vascular smooth-muscle cells, orhuman embryonic kidney 293 cells, using siRNAs was sufficient to block EGF- and c-Src-mediated ERK activation and cell migration.36,37 On the other hand, theectopic expression of Cat1 and Git1 in these same cells was found to extend EGF induced ERK activation.36 These findings suggested for the first time that Cat1 and Git1, atleast in certain contexts, could function as a signalingscaffold that connects growth factor receptor signaling tothe ERK pathway."
sparser
"The presented hMEC model was interrogated to ensure that it is able to reproduce some of the known global biological phenomena as previously observed experimentally ( xref ), including EGF-induced activation of Akt and Erk, EGF-independent regulation of Erk via activated Ras, integrin-dependent stimulation of Erk, Rac, and Cdc42, G-protein Coupled Receptor activation of adenylyl cyclase, as well as ErbB receptor dimerization hierarchy."
sparser
"To investigate whether catechol antagonizes against activations of EGFR, AKT, and ERK by EGF, HCC cells were pretreated with catechol 5 and 10 μM for 2 h in prior to stimulated with 100 ng/mL of EGF for 1 h, and p-EGFR, p-AKT, and p-ERK were detected by Western blotting and densitometric analysis."
sparser
"These experiments, comparing the sensitivity of ERK activation by IGF1, insulin, PDGF and EGF, showed that when PTEN expression was reduced by RNA interference, both cell types displayed normal activation of ERK by PDGF and EGF, but were significantly suppressed in their ability to activate ERK in response to IGF1 or insulin ( xref )."
sparser
"Notably, 11a-1 efficaciously attenuates cell viability and blocks EGF-induced ERK1/2 activation in H1975 lung cancer cells; abrogates ERK1/2 and AKT activation in SKBR3 breast cancer cells and suppresses cell growth in a 3D Matrigel environment; and inhibits oncogenic KITD814V-induced constitutive cell growth."
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"Pretreatment with the EGF receptor kinase inhibitor AG1478 had, remarkably, no significant effect on Erk1/2 activation induced by any of these adrenergic agonists (although it fully abolished EGF induced Erk1/2 activation), demonstrating absence of EGF receptor mediated transactivation."
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"Positive rate of ER-alpha36 was increased in high-stage (P =.03) and high-grade (P =.224) endometrial cancer; expression of ER-alpha36 and EGFR exhibited a significant positive correlation (r = 0.334, P =.025) and they showed substantial colocalization on the plasma membrane of glandular cells; phospho-extracellular signal regulated kinase positive rate in ER-alpha36 positive group and EGFR positive group was higher than that of ER-alpha36 negative group (P =.014) and EGFR negative group (P =.016); finally, ER-alpha36 mediated epidermal growth factor stimulated extracellular signal regulated kinase activation in Hec1A cells."
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"Overexpression of EGFR1 or HER2 as well as mutations that undermine the negative feedback regulation of the EGFR-ERK signaling pathway may transform the transient mode of the EGF induced ERK signaling to the sustained mode, and uncontrollably drive cells past the R-point [XREF_BIBR]."
sparser
"Furthermore, activation of ERK1/2 through EpEX-Fc and EGF in FaDu, Cal27, and Kyse30 cells was entirely blocked by an inhibitor of the upstream kinase MEK1 (AZD6244), whereas tyrosine kinase inhibitor (TKI) AG1478 entirely (Cal27) or partially (FaDu, Kyse30) blocked ERK1/2 activation by EpEX-Fc and EGF ( xref )."
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"Introduction of a SAICAR-insensitive or a non phosphorylatable PKM2 mutant inhibited the EGF stimulated ERK activation and consequent cancer cell proliferation, suggesting SAICAR induced PKM2 protein kinase activity is required for EGF mediated cancer cell proliferation [XREF_BIBR]."
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"Notably, EGF-mediated activation of ERK 1/2 was associated with a downregulation of endogenous CD protein level.The present work demonstrates, for the first time, a novel antiproliferative role of cathepsin D that may be exploited to improve neuroblastoma management and treatment."
sparser
"To further examine whether the promoting effect of mutant p53 on EGF-induced sustained ERK1/2 activation is due to enhanced phosphorylation of ERK1/2 or decreased dephosphorylation of phosphorylated-ERK1/2 (p-ERK1/2), p53-273H-expressing or control H1299 cells were pre-treated with EGF before the addition of MEK-1 (MAP ERK kinase) inhibitor U0126 at the different time points."
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"Interestingly, recent progress in understanding the key downstream effectors that mediate endocannabinoid signaling has implicated mammalian target of rapamycin complex 1 (mTORC1) rather than PI3K or ERK 103 as downstream signal effector; with biochemical and transcriptional experiments suggesting that PI3K activity is largely regulated by the EGF receptor, while the EGF and FGF receptors synergistically regulate the ERK pathway 168."
sparser
"In a study by Impagnatiello et al. [ xref ] indicating an anti-proliferative effects of the overexpressed Spry1 and Spry2 on endothelial cells in the presence of FGF, VEGF, and EGF, while FGF- and VEGF-induced activation of ERK were repressed by Sprouty, EGF-activated ERK was left unaffected."
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"The Src homology domain-2 containing tyrosine phosphatase-1 (SHP-1), highly expressed in hematopoietic cells, plays a positive role in epidermal growth factor-induced ERK1/2 activation and negative role in anti-apoptotic signaling pathway.23 Inhibition of the SHP-1 gene expression by miRNA has shown reduced cardiomyocyte apoptosis and increased cardio-protection through Akt activation in a rat model of cardiac ischemia-reperfusion injury.24 Combining gene therapies involves utilizing a hypoxia-inducible plasmid expressing both HO-1 and miSHP-1, demonstrating higher levels of HO-1 expression and miSHP-1 production in hypoxic cells compared to normoxic cells."
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"In addition, adenoviral overexpression of dominant negative ras (Ad.HA-Ras (N17)) partially inhibited the ATP- and PDBu induced activation of ERK1/2 and blocked ionomycin- and EGF stimulated ERK1/2, and inhibition of tyrosine kinases with AG-1478, an EGFR inhibitor, or the src family kinase inhibitor PP2 attenuated ATP stimulated ERK1/2 activation."
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"We confirmed that the silkworm carboxypeptidase inhibitor inhibited the expression of c-Myc through the MAPK/ERK pathway initiated by EGF/EGFR, thereby affecting the related cyclins and inhibiting the proliferation of gastric cancer cells.Currently, many scholars are focused on the discovery of lead compounds from active ingredients of natural products."
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"Because the combination of the PI-3-kinase and Mek and Erk inhibitors synergistically increased beta-casein promotor luciferase activity and because neither LY294002 nor Rapamycin affects EGF induced Erk activation, we conclude that the PI-3-kinase and Mek and Erk signaling pathways are independent and synergistic in their ability to block lactogenic differentiation in HC11 cells."
sparser
"In contrast to IGF-1, AICAR did not block epidermal growth factor (EGF)-dependent Raf-1 and Erk activation, but our results demonstrated that multiple Raf-1 upstream pathways induced by EGF were differentially affected by AICAR: inhibition of Ras activation and simultaneous induction of Ras-independent Raf activation."
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"Whereas seribantumab was effective at inhibiting HRG induced p-ErbB3 and p-Akt and erlotinib was effective at inhibiting EGF induced p-Erk, only the combination of both drugs shut down both pathways in the presence of HRG and EGF, which is qualitatively in agreement with the simulation results."
sparser
"In a study by Edwin et al. [ xref ], where Spry2 unexpectedly inhibited EGF activation of AKT and exhibited no significant effect on EGF activation of EGFR and ERK, they observed that Spry2 increases the amount and activity of PTEN that was found necessary for Sprouty to attenuate EGF-activated AKT and to inhibit cell proliferation."
sparser
"Since intracellular calcium levels fail to reach the near-millimolar concentrations required for calpain activation, epidermal growth factor (EGF) triggers the MAPK cascade and eventually activates ERK, which phosphorylates calpain at Ser50 and leads to calpain activation xref , xref ."
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"While several studies have suggested that Erk activation can be regulated through the PI-3-kinase pathway [XREF_BIBR, XREF_BIBR] our data demonstrated that EGF stimulation of Erk activation in HC11 mammary epithelial cells was not altered by blocking PI-3-kinase signaling with LY294002."
sparser
"The overexpression or reduction of IQGAP1 expression by siRNA both caused the activation of Erk2 by EGF or IGF-1 in MCF-7 cells to be reduced, probably due to an optimal level of intracellular IQGAP1 being necessary for maximal level of activation of Erk by EGF or IGF-1 [ xref ]."
sparser
"However, these modeling analyses also revealed non-obvious modes of potential regulation: (i) ERK activation is robust to parameter perturbation at high ligand doses, whereas Akt activation is not and (ii) PI-3K is a dominant factor for long-term but not short-term EGF-induced ERK activation."
sparser
"Celecoxib inhibited basal and EGF-stimulated proliferation, hypoxia-related HIF-1α recruitment/stabilization as well as hypoxia- and EGF-dependent activation of ERK and PI3K. Interestingly, celecoxib prevented EMT-related changes, as shown by modifications of β-catenin intracellular localization or vimentin and E-cadherin levels, as well as HT-29 invasiveness induced by hypoxia, EGF, or hypoxia plus EGF."
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"Since 2-APB blocks EGF induced immediate early gene expression without affecting EGF activation of the ERK and AKT signaling pathways, 2-APB represents a useful new probe for dissecting the roles of immediate early gene expression and ERK and AKT activation in downstream actions of EGF."
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"Overexpression of EGFR in MCF-7 cells confers estrogen independent growth, and studies using an MCF-7 cell line model of hormone resistance showed that EGF dependent activation of heterodimers of EGFR and HER1 and HER2 resulted in activation of the ERK pathway and increased cell proliferation."
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"Since the above data indicate that USP10 is involved in the EGF response, the next question was what molecular pathways might underlie this phenomenon.As EGF is a potent stimulator of the PI3K/AKT/mTOR and MAPK/ERK pathways and dysregulation of these pathways is common in CRC, we next tested whether USP10 knockout affects EGF-dependent activation of the PI3K/AKT/mTOR and MAPK/ERK signaling pathways.First, we examined EGF-induced phosphorylation of EGFR tyrosine 1068 (p-EGFR)."
sparser
"Niacin showed a selected additive effect on chemoattractant-induced activation of ERK1/2, JNK and PI3K pathways, but only the MEK inhibitor UO126 reduced niacin-mediated inhibition of macrophage chemotaxis, while activation of ERK1/2 by EGF alone did not inhibit fMLF-mediated migration of HEK293T cells co-expressing HCA2 and fMLF receptor FPR1."
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"Moreover, treatment of cells with epidermal growth factor (EGF) that activates MEK and ERK, as well as genetic ERK activation by a constitutively active MEK (MEK CA), increased T562 phosphorylation levels; pharmacological or genetic MEK inhibition using the selective U0126 inhibitor or byexpressing a dominant negative MEK mutant (MEK DN); and reduced T562 phosphorylation; finally, in Mfn1 -/- cells re-expressing the MFN1 T562A mutant, phosphorylation was undetectable even in the presence of EGF (XREF_FIG G)."
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"While GHR knockout is associated with diminished expression of the EGFR and a concomitant decrease in EGF signaling, GH overexpression results in EGFR overexpression with different effects depending on the signaling pathway analyzed : AKT and ERK1/2 pathways are induced by EGF, while STAT3 and STAT5 activation is heterologously desensitized."
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"By adding modifications to the established EGFR kinase inhibitor gefitinib, an approach to small molecule conjugates with a unique nuclear targeting peptoid sequence was tested in both human and murine breast tumor cell models for their capacity to inhibit EGF stimulated activation of ERK1/2 and STAT3."
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"We found that in HaCaT cells ADAM17 depletion reduces ERK1/2 phosphorylation, independent from the treatment with PsVs.To solidify the hypothesis that ADAM17 acts via the ERK signaling pathway in HPV16 infection and entry platform formation, we restored ERK activation by the addition of recombinant soluble form of the epidermal growth factor (EGF) which is one of the EGFR-activating ligands."
sparser
"Importantly, the kinetics of ERK1/2 activation by EGF (4 ng/ml) in gene-edited cells was essentially similar to that in parental cells ( xref and xref ), indicating that increased expression of endogenous mNG-KRAS did not affect signal transduction along the EGFR-ERK1/2 pathway."
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"Our previous studies have revealed that neuronal leucine-rich repeat 1 (NLRR1), a type І transmembrane protein, is associated with tumorigenesis by promoting cell proliferation through the activation of ERK mediated by EGF and IGF-1 (10) and negatively regulating anaplastic lymphoma kinase (ALK) (11) in NB, although the contribution of NLRR1 to other types of cancers is not understood."
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"To further investigate the bifurcation in EGF mediated activation of ERK1/2 versus STAT3 signaling upon subcellular compartmentalization of gefitinib, MDA-MB-468 cells were exposed to Gef-NArg, Gef-SV40-NArg, or gefitinib in a two-fold series of concentrations up to 1 muM for gefitinib or 5 muM for each peptoid conjugate (XREF_FIG)."
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"In fact, in addition to blocking DHT induced Erk activation, paxillin knockdown similarly blocks EGF induced Erk activation, indicating that paxillin functions downstream of the EGFR to regulate Erk activation in response to both direct (EGF) and indirect (DHT) EGFR activation [XREF_BIBR]."
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"Since EGF, a ligand of receptor tyrosine kinase, is widely reported to promote tumor growth, cell proliferation and apoptosis deregulation through activation of its downstream signaling, including MEK/ERK [25], we clarified whether 22-(4′py)-JA was able to suppress MEK/ERK signaling mediated by EGF."
sparser
"This is reinforced by the inhibition of clathrin-mediated endocytosis using two independent approaches, which did not significantly affect the time course of EGF-induced ERK1/2 activity ( xref ) and which confirmed that EGFR endocytosis is not an essential process for EGF-induced ERK1/2 activation in HeLa cells."
eidos
"Differences in the cell lines were generated by stimulation with either epidermal growth factor ( EGF ) ( E ) , which induces ERK and other kinase activity ,30 or anisomycin ( A ) , which has been reported to activate both the JNK and p38 MAPK cascades.31 Addition of U0126 , a MEK inhibitor ( U ) ,32 achieved inhibition of ERK ."
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"None of the other treatments had any significant effects on the uPAR induced response, although pertussis toxin did inhibit lysophosphatidic acid induced ERK activation, bisindolylmaleimide I and Go6983 inhibited PMA induced ERK activation, and PD98059 and U0126 inhibited platelet derived growth factor- and EGF induced ERK activation (data not shown)."
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"These data suggest that coactivation of both receptors enhances the release of sIL-6R from microglial cells.In DRG neurons, both hyper-IL-6 and EGF stimulation activated Stat3 and Erk1/2, but we were unable to show that IL-6-induced Stat3 activation was affected by blocking EGFR activation."
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"Widely expressed with highest levels in bone marrow, spleen, brain, testes, and embryonic brain, Abi1 may negatively regulate cell growth and transformation by interacting with the nonreceptor tyrosine kinases ABL1 and/or ABL2, thus regulating EGF induced Erk pathway activation and EGFR signaling."
sparser
"EGCG had no effect on activation of EGFR (tyr 1173 and tyr1045), pERK and pAKT by EGF, but specifically augmented ligand-induced downregulation of total EGFR protein, whereas erlotinib substantially abrogated the activation of pEGFR, pERK and pAKT by EGF without altering the total levels of EGFR protein."
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"However, while epidermal growth factor, which increases proliferation of PC12 cells, activates ERK1/2 only transiently, neural growth factor, which promotes their differentiation, induces a prolonged ERK1/2 activation [89], indicating that different patterns or duration of ERK1/2 activation are specifically and differently decoded by the cells."
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"However, the protein expression level of c-FOS is post-transcriptionally regulated by ERK activation kinetics, where transient ERK signals induced by EGF resulted in little induction of c-FOS, whereas sustained ERK activation by PDGF induced markedly higher amounts of the same protein [XREF_BIBR, XREF_BIBR]."
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"Since the results presented here indicate that ERK mediates positive regulation of PDX-1 expression by EGF and metformin has recently been shown to inhibit ERK activation in PDAC cells [XREF_BIBR, XREF_BIBR, XREF_BIBR], we hypothesized that the metformin inhibits PDX-1 expression by abrogating EGF induced ERK activation."
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"Metformin pretreatment also inhibited EGF stimulated ERK kinase activation, as evidenced by decreased phosphorylation of ERK at Thr201 and Tyr204 (XREF_FIG), consistent with the notion that metformin inhibits PDX-1 expression through a mechanism involving inhibition of EGF- stimulated ERK signaling (XREF_FIG)."
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"Given that metformin inhibited EGF stimulated ERK kinase activation, it is, thus, reasonable to speculate that metformin inhibits tumor cell proliferation through inhibiting EGF stimulated ERK kinase activation, leading to down-regulation of PDX-1 expression at post-translational level since ERK has kinase activity towards PDX-1 (XREF_FIG)."
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"EGF exposure resulted in a transient, significant induction of PKC (81kDa) and ERK (43kDa) activation, with maximal ~ 2-fold (p < = 0.001) and ~ 1.6-fold (p < = 0.001) increases seen at 15 and 30min, respectively (XREF_FIG); activation of the other PKC and ERK proteins remained unaffected (XREF_FIG)."
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"Stimulation of ERK signalling by EGF, which was particularly observed at the tegument, might be important during early host invasion during which the parasite will not only sense human EGF for the first time but must rapidly adapt to the host; thus, host mediated ERK activation might drive tegument remodelling ensuring parasite survival in addition to promoting cell growth/differentiation."
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"However, in breast cancer cells, abolishing PRMT5 mediated EGFR Arg1175 methylation increased EGF induced extracellular signal regulated kinase (ERK) activation by preventing the recruitment of Src homology 2 domain containing protein tyrosine phosphatase (SHP) 1 to EGFR, leading to enhanced cell proliferation, migration, and invasion of EGFR overexpressing tumor cells [XREF_BIBR]."
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"Results from this study show that triggering of GPR120 with EPA, DHA or AA in Caco-2 cells activated three independent intracellular signalling events; accumulation of cytosolic Ca 2+, EGF receptor- and Raf-1-dependent activation of MAP kinase ERK1/2, and EGF receptor- and Raf-1-independent inhibition of IL-1beta induced NF-kappaB activation."
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"Compounds 1 and 4 displayed strong cytotoxicity against three human tumor cell lines with GI50 values in the submicromolar range, whereas 2 showed subnanomolar activity as an inhibitor of EGFR-MAPK-AP1-mediated mitogenic signaling, causing inhibition of EGF mediated AP1 trans-activation and EGF mediated ERK activation and slight inhibition of EGF mediated JNK activation."
sparser
"Silencing QKI in the U343 glioblastoma cell line, results in miR-7 expression and cell cycle arrest, through a mechanism involving miR-7 negative regulation of epidermal growth factor (EGF) receptor (EGFR) protein levels, thus blunting the EGF-dependent ERK activation (Wang et al., xref )."
sparser
"Reminiscent of the distinct phenotypic outcomes observed in PC12 cells as a result of acute or sustained Erk activation by EGF or nerve growth factor (NGF) respectively xref , the authors showed that osteogenic differentiation of hMSCs was governed exclusively by differential activation of the PI3K pathway."
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"Thus, although PTHRP induced mitogenesis may occur through an ERK independent mechanism, the ability of PTHRP to potentiate the activation of ERK by EGF and IGF-1, together with the ability of cells to respond to autocrine PTHRP, could provide one explanation for the increased mitogenic responsiveness and reduced doubling times of MCF-7 cells overexpressing the PTHRP-R."
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"XREF_BIBR These observations are in agreement with previous reports conducted both invivo and invitro that have indicated that BMP-4 inhibits EGF stimulated ERK activation in isolated parietal cells XREF_BIBR and that prolonged overexpression of growth factors in the stomach of mice alters the normal architecture of the gastric mucosa, leading to increased ERK activation, loss of parietal cells, and foveolar hyperplasia."
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"Mitogenesis in response to EGF can not be studied in COS-7 cells as they are partially transformed, but it is known that picomolar EGF doses are able to activate the Ras and extracellular signal regulated kinase (ERK) signaling cascade, the central driver of cell proliferation in a PI3K dependent mode, in this cell type XREF_BIBR."
sparser
"Moreover, treatment of cells with epidermal growth factor (EGF) that activates MEK and ERK, as well as genetic ERK activation ( xref ) by a constitutively active MEK (MEK CA ) ( xref ), increased T562 phosphorylation levels; pharmacological or genetic MEK inhibition using the selective U0126 inhibitor or by expressing a dominant negative MEK mutant (MEK DN ); and reduced T562 phosphorylation; finally, in Mfn1 −/− cells re-expressing the MFN1 T562A mutant, phosphorylation was undetectable even in the presence of EGF ( xref G)."
sparser
"For instance, epidermal growth factor-induced transient ERK activation via the Raf-MEK-ERK axis induces proliferation in PC12 neuroendocrine cells, whereas nerve growth factor-induced prolonged ERK activation via the Raf-MEK-ERK axis leads to the differentiation of PC12 cells into sympathetic neuron-like cells [ xref , xref ]."
sparser
"Otherwise, a recent study described a regulatory signalling pathway of OSCC metastasis consisting of miR-491-5p and its downstream target, GIT1, which functions as a scaffold for EGF-induced ERK activation. xref In both studies, it would be interesting to analyse whether the decrease in activity of these downstream signalling cascades could be related to EGFR inhibition by miR-491-5p."
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"We defined the dynamic transcriptional effects elicited in MCF7, T-47D, and MDA-MB-436 breast cancer cell lines by nine regulators of growth and differentiation (17beta-estradiol, antiestrogens fulvestrant and tamoxifen, progestin R5020, antiprogestin RU486, all-trans-retinoic acid, epidermal growth factor, mitogen activated protein and extracellular signal regulated kinase 1/2 inhibitor U0126 and phorbol ester 12-O-tetradecanoylphorbol-13-acetate) and compared the patterns of gene regulation to published tumor expression profiles."
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"This sequence illustrates how non uniform EGF stimulation, which is visualized in the top row of images, can trigger a traveling wave of activated RAS that spreads over the plasma membrane (XREF_SUPPLEMENTARY) and that produces a transient gradient of ERK activity within the cell, which is visualized in the bottom row of images."
sparser
"The augmented cellular endogenous forces induce cell-matrix adhesion kinase signaling, ROCK-mediated disruption of adherens junctions and growth-factor-dependent ERK activation, resulting in: (i) tumor cell proliferation, (ii) disruption of basal polarity, (iii) abrogation of glandular lumen formation, and (iv) remodeling of mammary tissue architecture [ xref , xref ]."
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"The role played by Cdc42 in regulating the timing of EGF receptor-Cbl interactions is underscored by the fact that constitutively active Cdc42 (F28L), by persistently blocking the binding of Cbl to these receptors, leads to their aberrant accumulation and sustained EGF stimulated ERK activation, thus resulting in cellular transformation."
sparser
"Thus, although PTHRP-induced mitogenesis may occur through an ERK-independent mechanism, the ability of PTHRP to potentiate the activation of ERK by EGF and IGF-1, together with the ability of cells to respond to autocrine PTHRP, could provide one explanation for the increased mitogenic responsiveness and reduced doubling times of MCF-7 cells overexpressing the PTHRP-R."
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"To test whether inhibition of endocytosis affects EGF-induced ERK1/2 activity, the effects of siRNA knockdown of clathrin heavy chain (CHC) and a small-molecule Dyngo-4a, treatments known to inhibit clathrin-mediated endocytosis of EGFR (Huang et al., 2004; Pinilla-Macua and Sorkin, 2015), on the time course of ERK1/2 activation were tested."
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"This is reinforced by the inhibition of clathrin-mediated endocytosis using two independent approaches, which did not significantly affect the time course of EGF-induced ERK1/2 activity (Fig. 8) and which confirmed that EGFR endocytosis is not an essential process for EGF-induced ERK1/2 activation in HeLa cells."
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"Consistent with these previous results, immunoblotting of phosphorylated ERK1/2 in cells stimulated with EGF for 10, 20, 30 and 60 min showed that EGF stimulation induced a peak activation of ERK1/2 at 10 min, which quickly dropped to ~ 10% of its peak level at 20 min and remained at low levels afterwards (XREF_FIG)."
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"Our results show that under both continuous and pulse-chase EGF conditions, inhibition of the ALIX supported MVB sorting of activated EGFR by each of the three different approaches employed converts the sharp peak kinetics of the EGF induced activation of ERK1/2 into a slow slope kinetics, lengthening the EGF induced ERK1/2 activation from < 20 min to> 2 h."
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"The overexpression or reduction of IQGAP1 expression by siRNA both caused the activation of Erk2 by EGF or IGF-1 in MCF-7 cells to be reduced, probably due to an optimal level of intracellular IQGAP1 being necessary for maximal level of activation of Erk by EGF or IGF-1 [XREF_BIBR]."
sparser
"None of the other treatments had any significant effects on the uPAR-induced response, although pertussis toxin did inhibit lysophosphatidic acid–induced ERK activation, bisindolylmaleimide I and Gö6983 inhibited PMA-induced ERK activation, and PD98059 and U0126 inhibited platelet-derived growth factor– and EGF-induced ERK activation (data not shown)."
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"Our finding that reconstitution of SHP2 Y542F in SHP2 depleted H1666 cells rescued ERK phosphorylation as efficiently as SHP2 WT suggests that SHP2 Y542 phosphorylation is dispensable for SHP2 mediated activation of ERK, consistent with previous findings regarding EGF mediated ERK activation in 3T3 fibroblasts."
sparser
"Inhibition of ERK activity by U0126 or suppression of Rac1 activity by ectopic expression of inactive mutant form of Rac1 (Rac1-T17N) significantly prevents EGF-induced cell migration, suggesting that EGF-induced ERK and Rac1 activation was responsible for the migration of these cancer cells."
sparser
"Initial insight into this specificity dilemma came from observations that PC-12 cells proliferated after a transient ERK activation by epidermal growth factor (EGF), but differentiated after a sustained ERK activation by nerve growth factor (NGF), showing that the duration of ERK signaling is critical for cell fate decisions ( xref )."
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"A well-known example of a FRET based activity reporter is the extracellular signal regulated kinase activity reporter (EKAR) [XREF_BIBR], which has been used to study oscillatory EGF mediated ERK activation and relationships between ERK activity and nucleocytoplasmic shuttling [XREF_BIBR, XREF_BIBR]."
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"From these considerations, we would predict that an EGF sinewave with average EGF concentration of between 0.02 and 0.04 Kd, and frequency of 2.5 × 10 –3 × 10 rad/s (i.e., a period of 0.5 h to 4 h) would produce a DC value of ERK* of 0.11–0.16 and an ERK* maximum peak value close to 1."