Open AccessMEK/ERK regulates adherens junctions and migration through Rac1
Author(s) -
Ray Ramesh M.,
Vaidya Rajiv J.,
Johnson Leonard R.
Publication year - 2007
Publication title -
cell motility and the cytoskeleton
Language(s) - English
Resource type - Journals
eISSN - 1097-0169
pISSN - 0886-1544
DOI - 10.1002/cm.20172
Subject(s) - microbiology and biotechnology , rac1 , biology , polyamine , mapk/erk pathway , adherens junction , cell migration , ornithine decarboxylase , intracellular , cell , biochemistry , cadherin , signal transduction , enzyme
Polyamine depletion with the ornithine decarboxylase inhibitor α‐difluoromethyl ornithine (DFMO), prevents Rac1 activation causing the formation of a thick actin cortex at the cell periphery and inhibits migration of intestinal epithelial cells. In the present study, we demonstrate that MEK activation by EGF increased Rac1 activation, dissociation of intercellular contacts, and migration in both control and polyamine‐depleted cells, while U0126, a specific inhibitor of MEK1, prevented disruption of junctions as well as EGF‐induced Rac1 activation. Constitutively active MEK1 (CA‐MEK) expression altered cell–cell contacts in control and polyamine depleted cells. The expression of constitutively active Rac1 (CA‐Rac1) restored β‐catenin to the cell periphery and prevented the formation of actin cortex and caused the appearance of F‐actin stress fibers in polyamine‐depleted cells. Inhibition of Rac activation by NSC23766, a specific inhibitor of Tiam1, an upstream guanidine nucleotide exchange factor for Rac1, reproduced the β‐catenin localization and actin structure of polyamine‐depleted cells. Tiam1 localized more extensively with β‐catenin at the cell periphery in CA‐Rac1 cells compared to vector cells. Polyamine depletion decreased the expression of E‐cadherin to a greater extent compared to β‐catenin. Subcellular fractionation further confirmed our immuno‐localization and western blotting observations. These data suggest that EGF acting through MEK1/ERK to activate Rac1 regulates cell–cell contacts. Thus, decreased migration in polyamine depleted cells may be due to the inhibition of Tiam1 activation of Rac1 and the subsequent decreased expression of β‐catenin and E‐cadherin leading to reduced cell–cell contacts. Cell Motil. Cytoskeleton 2007. © 2006 Wiley‐Liss, Inc.