An essential role for Src kinase in ErbB receptor signaling through the MAPK pathway.

摘要: ErbB receptor tyrosine kinases are activated by multiple ligands such as epidermal growth factor (EGF) and neuregulins (NRGs), leading to stimulation of intracellular signaling pathways, including the mitogen-activated protein kinase (MAPK) cascade. We show here that Src is essential for rapid EGF- NRG-induced MAPK activation when breast carcinoma cell lines T47D SKBR3 stimulated with low concentrations ligand. In presence pharmacological inhibitor CGP77675, which specifically blocks activity family kinases, ligand-induced was almost completely blocked at 5 min. Although this block only transient, inactivation suppressed transcription from a MAPK-responsive promoter. At molecular level, initial inhibition correlated impaired Shc phosphorylation. Surprisingly, affected neither association receptors nor phosphorylation receptor-bound Shc. Thus, requires engagement novel Src-dependent route MAPK, trigger its subsequent efficient transcription.