PAK1 Phosphorylation of MEK1 Regulates Fibronectin-stimulated MAPK Activation

Overview

Journal J Cell Biol

Specialty Cell Biology

Date 2003 Jul 24

PMID 12876277

Citations 129

Authors

Jill K Slack-Davis

Scott T Eblen

Maja Zecevic

Scott A Boerner

Adel Tarcsafalvi

H Bruce Diaz

Mark S Marshall

Michael J Weber

J Thomas Parsons

Andrew D Catling

Affiliations

Soon will be listed here.

Abstract

Activation of the Ras-MAPK signal transduction pathway is necessary for biological responses both to growth factors and ECM. Here, we provide evidence that phosphorylation of S298 of MAPK kinase 1 (MEK1) by p21-activated kinase (PAK) is a site of convergence for integrin and growth factor signaling. We find that adhesion to fibronectin induces PAK1-dependent phosphorylation of MEK1 on S298 and that this phosphorylation is necessary for efficient activation of MEK1 and subsequent MAPK activation. The rapid and efficient activation of MEK and phosphorylation on S298 induced by cell adhesion to fibronectin is influenced by FAK and Src signaling and is paralleled by localization of phospho-S298 MEK1 and phospho-MAPK staining in peripheral membrane-proximal adhesion structures. We propose that FAK/Src-dependent, PAK1-mediated phosphorylation of MEK1 on S298 is central to the organization and localization of active Raf-MEK1-MAPK signaling complexes, and that formation of such complexes contributes to the adhesion dependence of growth factor signaling to MAPK.

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