MEKK1 Regulates Calpain-dependent Proteolysis of Focal Adhesion Proteins for Rear-end Detachment of Migrating Fibroblasts

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2003 Jul 4

PMID 12839996

Citations 50

Authors

Bruce D Cuevas

Amy N Abell

James A Witowsky

Toshiaki Yujiri

Nancy Lassignal Johnson

Kamala Kesavan

Marti Ware

Peter L Jones

Scott A Weed

Roberta L DeBiasi

Yoshitomo Oka

Kenneth L Tyler

Gary L Johnson

Affiliations

Soon will be listed here.

Abstract

Herein, we define how MEKK1, a MAPK kinase kinase, regulates cell migration. MEKK1 is associated with actin fibers and focal adhesions, localizing MEKK1 to sites critical in the control of cell adhesion and migration. EGF-induced ERK1/2 activation and chemotaxis are inhibited in MEKK1-/- fibroblasts. MEKK1 deficiency causes loss of vinculin in focal adhesions of migrating cells, increased cell adhesion and impeded rear-end detachment. MEKK1 is required for activation of the cysteine protease calpain and cleavage of spectrin and talin, proteins linking focal adhesions to the cytoskeleton. Inhibition of ERK1/2 or calpain, but not of JNK, mimics MEKK1 deficiency. Therefore, MEKK1 regulates calpain-mediated substratum release of migrating fibroblasts.

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