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

Article Details

Citation

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

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

J Cell Biol. 2005 Aug 1;170(3):465-76.

PubMed ID
16061695 [ View in PubMed
]
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.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Calcium and integrin-binding protein 1Q99828Details
Serine/threonine-protein kinase PAK 1Q13153Details