title: Contra-regulation of calcium- and integrin-binding protein 1-induced cell migration on fibronectin by PAK1 and MAP kinase signaling.
abstract: Calcium- and integrin-binding protein 1 (CIB1) has been shown to be involved in cell spreading and migration. The signaling events regulated by CIB1 during cell migration are poorly understood. Here we found that accumulation of CIB1 at the tip of the filopodia requires an intact cytoskeleton. Depletion of CIB1 using shRNA affects formation of FAK- and phosphotyrosine-rich focal adhesions without affecting stress fiber formation. Overexpression of CIB1 results in cell migration on fibronectin and Erk1/2 MAP kinase activation. CIB1-induced cell migration is dependent upon Erk1/2 activation, since it is inhibited by the MEK-specific inhibitor PD98059. Furthermore, CIB1-induced cell migration, as well as Erk1/2 activation, is dependent on PKC, Src family kinases as well as PI-3 kinase as it is inhibited by bisindolylmaleimide 1, PP2, and wortmannin, respectively, in a dose-dependent manner. Co-expression of dominant-negative Cdc42 completely abolished CIB1-induced cell migration. Additionally, co-expression of constitutively active, but not dominant negative PAK1, a CIB1 binding protein, inhibited CIB1-induced cell migration. These results suggest that CIB1 positively regulates cell migration and is necessary for the recruitment of FAK to the focal adhesions. Furthermore, CIB1-induced cell migration is dependent on MAP kinase signaling and its function is attenuated by PAK1.
authors: Department of Biological Sciences, University of Delaware, Newark, Delaware 19716, USA.
authors: Meghna U
authors: MU
authors: Naik
authors: Ulhas P
authors: UP
authors: Naik
mesh_terms: D000818:Animals; D016466:CHO Cells; D002135:Calcium-Binding Proteins / Q000502:physiology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D006224:Cricetinae; D003412:Cricetulus; D004789:Enzyme Activation; D005353:Fibronectins / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D022001:Focal Adhesions; D006801:Humans; D020935:MAP Kinase Signaling System; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D054462:p21-Activated Kinases / Q000378:metabolism*
chemical_list: C109198:CIB1 protein, human; D002135:Calcium-Binding Proteins; D005353:Fibronectins; D019869:Phosphatidylinositol 3-Kinases; C515903:PAK1 protein, human; D054462:p21-Activated Kinases