Roles of Gab1 and SHP2 in Paxillin Tyrosine Dephosphorylation and Src Activation in Response to Epidermal Growth Factor

Yuan Ren, Songshu Meng, Lin Mei, Z. Joe Zhao, Richard Jove, Jie Wu

Research output: Contribution to journalArticle

127 Citations (Scopus)

Abstract

Epidermal growth factor (EGF) induces paxillin tyrosine dephosphorylation and Src activation, but the signaling pathways that mediate these responses were largely undefined. We found that Gab1, a docking protein for the SHP2 protein-tyrosine phosphatase in EGF-stimulated cells, was associated with paxillin. SHP2 dephosphorylated paxillin and caused dissociation of Csk, a negative regulator of Src, from paxillin but had no effect on paxillin-Src association. A lower level of Src Tyr-530 phosphorylation was detected in paxillin-associated Src in EGF-stimulated cells. Expression of an SHP2 binding defective mutant of Gab1 (Gab1FF) or a catalytically inactive mutant of SHP2 (SHP2DN) prevented paxillin tyrosine dephosphorylation and Src activation induced by EGF. Importantly, Gab1FF blocked paxillin-SHP2 complex formation, Src Tyr-530 dephosphorylation, Erk activation, and cell migration induced by EGF. Inhibition of Src tyrosine kinase activity abrogated EGF-stimulated Erk activation and cell migration. Together, these results reveal that Gab1 recruits SHP2 to dephosphorylate paxillin, leading to dissociation of Csk from the paxillin-Src complex and Src activation and that Src is an SHP2 effector involved in EGF-stimulated Erk activation and cell migration.

Original languageEnglish (US)
Pages (from-to)8497-8505
Number of pages9
JournalJournal of Biological Chemistry
Volume279
Issue number9
DOIs
StatePublished - Feb 27 2004

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Paxillin
Epidermal Growth Factor
Tyrosine
Chemical activation
Cell Movement
Non-Receptor Type 11 Protein Tyrosine Phosphatase
Phosphorylation
Protein Tyrosine Phosphatases
src-Family Kinases
Association reactions

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Roles of Gab1 and SHP2 in Paxillin Tyrosine Dephosphorylation and Src Activation in Response to Epidermal Growth Factor. / Ren, Yuan; Meng, Songshu; Mei, Lin; Zhao, Z. Joe; Jove, Richard; Wu, Jie.

In: Journal of Biological Chemistry, Vol. 279, No. 9, 27.02.2004, p. 8497-8505.

Research output: Contribution to journalArticle

Ren, Yuan ; Meng, Songshu ; Mei, Lin ; Zhao, Z. Joe ; Jove, Richard ; Wu, Jie. / Roles of Gab1 and SHP2 in Paxillin Tyrosine Dephosphorylation and Src Activation in Response to Epidermal Growth Factor. In: Journal of Biological Chemistry. 2004 ; Vol. 279, No. 9. pp. 8497-8505.
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