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

Abstract:

: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 kinase is essential for rapid EGF- and NRG-induced MAPK activation when the breast carcinoma cell lines T47D and SKBR3 are stimulated with low concentrations of ligand. In the presence of the pharmacological inhibitor CGP77675, which specifically blocks the activity of Src family kinases, ligand-induced MAPK activation was almost completely blocked at 5 min. Although this block was only transient, inactivation of Src suppressed ligand-induced transcription from a MAPK-responsive promoter. At the molecular level, the initial inhibition of MAPK by Src inactivation correlated with impaired ligand-induced Shc phosphorylation. Surprisingly, Src inhibition affected neither association of Shc with ErbB receptors nor phosphorylation of receptor-bound Shc. Thus, ErbB signaling requires the engagement of a novel Src-dependent route to MAPK, to trigger its rapid activation and subsequent efficient stimulation of transcription.

journal_name

Exp Cell Res

authors

Olayioye MA,Badache A,Daly JM,Hynes NE

doi

10.1006/excr.2001.5242

keywords:

subject

Has Abstract

pub_date

2001-07-01 00:00:00

pages

81-7

issue

1

eissn

0014-4827

issn

1090-2422

pii

S0014-4827(01)95242-5

journal_volume

267

pub_type

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