Premium
Regulation of actin function by protein kinase A‐mediated phosphorylation of Limk1
Author(s) -
Nadella Kiran S,
Saji Motoyasu,
Jacob Naduparambil K,
Pavel Emilia,
Ringel Matthew D,
Kirschner Lawrence S
Publication year - 2009
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/embor.2009.58
Subject(s) - cofilin , microbiology and biotechnology , phosphorylation , protein kinase a , kinase , rho associated protein kinase , biology , actin cytoskeleton , chemistry , cytoskeleton , cell , biochemistry
Proper regulation of the cAMP‐dependent protein kinase (protein kinase A, PKA) is necessary for cellular homeostasis, and dysregulation of this kinase is crucial in human disease. Mouse embryonic fibroblasts (MEFs) lacking the PKA regulatory subunit Prkar1a show altered cell morphology and enhanced migration. At the molecular level, these cells showed increased phosphorylation of cofilin, a crucial modulator of actin dynamics, and these changes could be mimicked by stimulating the activity of PKA. Previous studies of cofilin have shown that it is phosphorylated primarily by the LIM domain kinases Limk1 and Limk2, which are under the control of the Rho GTPases and their downstream effectors. In Prkar1a −/− MEFs, neither Rho nor Rac was activated; rather, we showed that PKA could directly phosphorylate Limk1 and thus enhance the phosphorylation of cofilin. These data indicate that PKA is crucial in cell morphology and migration through its ability to modulate directly the activity of LIM kinase.