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• W2063808445 endingPage "4633" @default.
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• W2063808445 abstract "Here we address the molecular mechanism of serum-independent survival and growth of human bladder carcinoma cell line 5637. Serum starvation promoted tyrosine phosphorylation of a 145-kDa protein and activation of the tyrosine kinase Src and the receptor for epidermal growth factor (EGFR) over a slow time course (&gt;8 hours). The phosphorylated 145-kDa protein was identified as the β-subunit of c-Met/hepatocyte growth factor (HGF) receptor, p145met, in which tyrosine residues 1003, 1234, and 1235 were phosphorylated. Inhibitors of Src (PP2, SU6656) or EGFR (AG99), but not p145met (K252a), effectively blocked tyrosine phosphorylation of p145met and promoted cell death accompanied by activation of caspase-like proteases. Conditioned medium from the serum-starved 5637 cells or purified EGF readily promoted the activation of Src and EGFR, and tyrosine phosphorylation of p145met in normally grown 5637 cells, suggesting that autocrine signaling of EGFR ligands is responsible for signal transduction events in serum-starved cells. Consistent with this idea, a monoclonal antibody against EGFR that would interfere with the ligand binding to EGFR blocked tyrosine phosphorylation events and promoted the caspase activation and cell death in serum-free conditions. Such apoptotic cell death was also induced by pretreatment of cells with a high concentration of HGF that downregulated endogenous p145met. Nevertheless, Cu2+ ions, competitive inhibitors for HGF-binding to p145met, did not show any effect on cellular functions in serum-free conditions. These results suggest that the serum-independent growth of 5637 cells involves the transmembrane signaling cascade via EGFR ligand(s) (but not HGF), EGFR, Src and p145met." @default.
• W2063808445 created "2016-06-24" @default.
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• W2063808445 date "2006-11-15" @default.
• W2063808445 modified "2023-09-28" @default.
• W2063808445 title "Tyrosine phosphorylation of p145met mediated by EGFR and Src is required for serum-independent survival of human bladder carcinoma cells" @default.
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• W2063808445 doi "https://doi.org/10.1242/jcs.03236" @default.
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