Teckchandani Anjali M, Panetti Tracee S, Tsygankov Alexander Y
Department of Microbiology and Immunology, Temple University School of Medicine, 3400 N. Broad Street, Philadelphia, PA 19140, USA.
Exp Cell Res. 2005 Jul 1;307(1):247-58. doi: 10.1016/j.yexcr.2005.03.010. Epub 2005 Apr 15.
Cellular events like cell adhesion and migration involve complex rearrangements of the actin cytoskeleton. We have previously shown that the multidomain adaptor protein c-Cbl facilitates actin cytoskeletal reorganizations that result in the adhesion of v-Abl-transformed NIH 3T3 fibroblasts. In this report, we demonstrate that c-Cbl also enhances migration of v-Abl-transformed NIH 3T3 fibroblasts. This effect of c-Cbl depends on its tyrosine phosphorylation, specifically on phosphorylation of its Tyr-731, which is required for binding of PI-3' kinase to c-Cbl. Furthermore, we demonstrate that the effect of c-Cbl on migration of v-Abl-transformed fibroblasts is mediated by active PI-3' kinase and the small GTPase Rac1. Our results also indicate that ubiquitin ligase activity of c-Cbl is required, while spatial localization of c-Cbl to the pseudopodia is not required for the observed effects of c-Cbl on cell migration.
