Src phosphorylates Grb2-associated binder 1 upon hepatocyte growth factor stimulation

¹Department of Life Sciences and the Graduate Institute of Biomedical Sciences, National Chung Hsing University, Taichung 40227, Taiwan.

|August 28, 2003

Summary

Src kinases enhance hepatocyte growth factor (HGF)-induced Gab1 phosphorylation, a key step in HGF signaling. This study reveals Src

Area of Science:

Background:

Grb2-associated binder 1 (Gab1) is crucial for hepatocyte growth factor (HGF) signaling.
Gab1 undergoes rapid tyrosine phosphorylation upon HGF stimulation.

Purpose of the Study:

To investigate the role of Src family kinases in HGF-induced Gab1 phosphorylation.
To elucidate the mechanism by which Src influences Gab1 activity.

Main Methods:

Utilized Src/Yes/Fyn null mouse embryo-derived cells and wild-type counterparts.
Employed Src kinase-deficient mutants, constitutively active Src mutants, and Src inhibitor PP1.
Performed in vitro kinase assays with purified Gab1.
Assessed HGF-induced activation of ERK and AKT.

Main Results:

Gab1 tyrosine phosphorylation was reduced by ~40% in Src/Yes/Fyn null cells compared to wild-type cells upon HGF stimulation.
Overexpression of wild-type Src enhanced HGF-induced Gab1 phosphorylation, while kinase-deficient Src or PP1 treatment suppressed it.
Constitutively active Src mutants (Y527F, v-Src) increased Gab1 phosphorylation independently of HGF.
Src directly interacted with and phosphorylated Gab1 in vitro.
Src-mediated Gab1 phosphorylation potentiated HGF-induced ERK and AKT activation.

Conclusions:

Src family kinases play a significant role in regulating Gab1 phosphorylation in response to HGF.
Src directly phosphorylates Gab1, influencing downstream signaling pathways like ERK and AKT.
This study establishes a novel function for Src in the HGF/Gab1 signaling axis.

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