Open AccessCaMK‐II promotes focal adhesion turnover and cell motility by inducing tyrosine dephosphorylation of FAK and paxillin
Author(s) -
Easley Charles A.,
Brown Claire M.,
Horwitz Alan F.,
Tombes Robert M.
Publication year - 2008
Publication title -
cell motility and the cytoskeleton
Language(s) - English
Resource type - Journals
eISSN - 1097-0169
pISSN - 0886-1544
DOI - 10.1002/cm.20294
Subject(s) - focal adhesion , paxillin , ptk2 , microbiology and biotechnology , biology , motility , population , tyrosine , cell adhesion , tyrosine phosphorylation , phosphorylation , cell , biochemistry , protein kinase a , mitogen activated protein kinase kinase , demography , sociology
Transient elevations in Ca 2+ have previously been shown to promote focal adhesion disassembly and cell motility through an unknown mechanism. In this study, evidence is provided to show that CaMK‐II, a Ca 2+ /calmodulin dependent protein kinase, influences fibroblast adhesion and motility. TIRF microscopy reveals a dynamic population of CaMK‐II at the cell surface in migrating cells. Inhibition of CaMK‐II with two mechanistically distinct, membrane permeant inhibitors (KN‐93 and myr‐AIP) freezes lamellipodial dynamics, accelerates spreading on fibronectin, enlarges paxillin‐containing focal adhesions and blocks cell motility. In contrast, constitutively active CaMK‐II is not found at the cell surface, reduces cell attachment, eliminates paxillin from focal adhesions and decreases the phospho‐tyrosine levels of both FAK and paxillin; all of these events can be reversed with myr‐AIP. Thus, both CaMK‐II inhibition and constitutive activation block cell motility through over‐stabilization or destabilization of focal adhesions, respectively. Coupled with the existence of transient Ca 2+ elevations and a dynamic CaMK‐II population, these findings provide the first direct evidence that CaMK‐II enables cell motility by transiently and locally stimulating tyrosine dephosphorylation of focal adhesion proteins to promote focal adhesion turnover. Cell Motil. Cytoskeleton, 2008. © 2008 Wiley‐Liss, Inc.