c-Cbl regulates migration of v-Abl-transformed NIH 3T3 fibroblasts via Rac1.
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.
Teckchandani
Anjali M
AM
Department of Microbiology and Immunology, Temple University School of Medicine, 3400 N. Broad Street, Philadelphia, PA 19140, USA.
Panetti
Tracee S
TS
Tsygankov
Alexander Y
AY
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D002461:Cell Line, Transformed; D002465:Cell Movement; D002472:Cell Transformation, Viral; D005347:Fibroblasts / Q000502:physiology*; D019084:Fluorescent Antibody Technique, Indirect; D051379:Mice; D018613:Microscopy, Confocal; D041681:NIH 3T3 Cells; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000502:physiology*; D016315:Proto-Oncogene Proteins c-abl / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D014452:Ubiquitins / Q000378:metabolism; D000077191:Wortmannin; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*
D000730:Androstadienes; D011518:Proto-Oncogene Proteins; D014452:Ubiquitins; D014443:Tyrosine; D044767:Ubiquitin-Protein Ligases; D019869:Phosphatidylinositol 3-Kinases; D016315:Proto-Oncogene Proteins c-abl; D020830:rac1 GTP-Binding Protein; D000077191:Wortmannin