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MEKK1 regulates calpain‐dependent proteolysis of focal adhesion proteins for rear‐end detachment of migrating fibroblasts
Author(s) -
Cuevas Bruce D.,
Abell Amy N.,
Witowsky James A.,
Yujiri Toshiaki,
Johnson Nancy Lassignal,
Kesavan Kamala,
Ware Marti,
Jones Peter L.,
Weed Scott A.,
DeBiasi Roberta L.,
Oka Yoshitomo,
Tyler Kenneth L.,
Johnson Gary L.
Publication year - 2003
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/cdg322
Subject(s) - focal adhesion , calpain , vinculin , microbiology and biotechnology , paxillin , actin , chemistry , cell migration , actin cytoskeleton , mechanotransduction , cytoskeleton , integrin , biology , signal transduction , cell , biochemistry , enzyme
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.