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PMID: 16061695 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, P.H.S.

Essential role of CIB1 in regulating PAK1 activation and cell migration.

The Journal of cell biology ·Vol. 170 ·No. 3 ·2005-08-01 ·Pages 465-76

Leisner TM, Liu M, Jaffer ZM, Chernoff J, Parise LV

Abstract

p21-activated kinases (PAKs) regulate many cellular processes, including cytoskeletal rearrangement and cell migration. In this study, we report a direct and specific interaction of PAK1 with a 22-kD Ca2+-binding protein, CIB1, which results in PAK1 activation both in vitro and in vivo. CIB1 binds to PAK1 within discrete regions surrounding the inhibitory switch domain in a calcium-dependent manner, providing a potential mechanism of CIB1-induced PAK1 activation. CIB1 overexpression significantly decreases cell migration on fibronectin as a result of a PAK1-and LIM kinase-dependent increase in cofilin phosphorylation. Conversely, the RNA interference-mediated depletion of CIB1 increases cell migration and reduces normal adhesion-induced PAK1 activation and cofilin phosphorylation. Together, these results demonstrate that endogenous CIB1 is required for regulated adhesion-induced PAK1 activation and preferentially induces a PAK1-dependent pathway that can negatively regulate cell migration. These results point to CIB1 as a key regulator of PAK1 activation and signaling.

MeSH Terms
Actin Depolymerizing Factors Animals Binding Sites Blood Platelets Calcium/metabolism Calcium-Binding Proteins/genetics,metabolism Cell Movement/physiology Cells, Cultured Enzyme Activation Fibronectins/metabolism Humans Mice Microfilament Proteins/metabolism Phosphorylation Protein Binding Protein Serine-Threonine Kinases/genetics,metabolism Protein Structure, Tertiary Signal Transduction/physiology cdc42 GTP-Binding Protein/metabolism p21-Activated Kinases rho GTP-Binding Proteins/metabolism
Chemicals
Actin Depolymerizing Factors CIB1 protein, human Calcium-Binding Proteins Fibronectins Microfilament Proteins PAK1 protein, human Pak1 protein, mouse Protein Serine-Threonine Kinases p21-Activated Kinases cdc42 GTP-Binding Protein rho GTP-Binding Proteins Calcium
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Leisner Tina M
Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Liu Mingjuan
Jaffer Zahara M
Chernoff Jonathan
Parise Leslie V
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.200502090
Published
2005-08-01
Pages
465-76
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2171473
Subset
IM
Grants
NHLBI NIH HHS · 2P01 HL 45100 · United States
NIGMS NIH HHS · R01 GM 54168 · United States
NCI NIH HHS · T32 CA009156 · United States
NCI NIH HHS · CA09156 · United States
NHLBI NIH HHS · P01 HL045100 · United States
NIGMS NIH HHS · R01 GM054168 · United States
External Links
PubMed source DOI: 10.1083/jcb.200502090 PMC Full Text View journal details
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