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PMID: 19424295 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Regulation of actin function by protein kinase A-mediated phosphorylation of Limk1.

EMBO reports ·Vol. 10 ·No. 6 ·2009-06-00 ·Pages 599-605

Nadella KS, Saji M, Jacob NK, Pavel E, Ringel MD, Kirschner LS

Abstract

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.

MeSH Terms
Actin Cytoskeleton/metabolism Actins/metabolism Animals Cyclic AMP-Dependent Protein Kinase RIalpha Subunit/metabolism Enzyme Activation HeLa Cells Humans Lim Kinases/metabolism Mice Models, Biological Phosphorylation
Chemicals
Actins Cyclic AMP-Dependent Protein Kinase RIalpha Subunit Prkar1a protein, mouse Lim Kinases Limk1 protein, mouse
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Nadella Kiran S
Department of Molecular Virology, Immunology & Medical Genetics, The Ohio State University, 420 West 12th Avenue, TMRF 544, Columbus, Ohio 43210, USA.
Saji Motoyasu
Jacob Naduparambil K
Pavel Emilia
Ringel Matthew D
Kirschner Lawrence S
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Article Info
Journal
EMBO reports
Abbr.
EMBO Rep
ISSN
1469-3178
DOI
10.1038/embor.2009.58
Published
2009-06-00
Epub
2009-00-08
Pages
599-605
Language
English
Region
England
NLM ID
100963049
PMCID
PMC2711837
Subset
IM
Grants
NCI NIH HHS · R01 CA112268 · United States
NCI NIH HHS · CA16058 · United States
NICHD NIH HHS · K22 HD001323 · United States
NCI NIH HHS · R01 CA102572 · United States
NCI NIH HHS · CA112268 · United States
NICHD NIH HHS · HD01323 · United States
NCI NIH HHS · P30 CA016058 · United States
NCI NIH HHS · CA102572 · United States
Corrections
ErratumIn
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External Links
PubMed source DOI: 10.1038/embor.2009.58 PMC Full Text View journal details
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