Synergistic promotion of c-Src activation and cell migration by Cas and AND-34/BCAR3.
The adapter molecule p130Cas (Cas) plays a role in cellular processes such as proliferation, survival, cell adhesion, and migration. The ability of Cas to promote migration has been shown to be dependent upon its carboxyl terminus, which contains a bipartite binding site for the protein tyrosine kinase c-Src (Src). The association between Src and Cas enhances Src kinase activity, and like Cas, Src plays an important role in cell proliferation and migration. In this study, we show that Src and Cas function cooperatively to promote cell migration in a manner that depends upon kinase-active Src. Another carboxyl-terminal binding partner of Cas, AND-34/BCAR3 (AND-34), functions synergistically with Cas to enhance Src activation and cell migration. The carboxyl-terminal guanine nucleotide exchange factor domain of AND-34, as well as the activity of its putative target Rap1, contribute to these events. A mechanism through which AND-34 may regulate Cas-dependent cell migration is suggested by the finding that Cas becomes redistributed from focal adhesions to lamellipodia located at the leading edge of AND-34 overexpressing cells. These data thus provide insight into how Cas and AND-34 may function together to stimulate Src signaling pathways and promote cell migration.
Department of Microbiology and Cancer Center, University of Virginia Health System, Charlottesville, Virginia 22908-0735, USA.
Rebecca B
RB
Riggins
Lawrence A
LA
Quilliam
Amy H
AH
Bouton
D048868:Adaptor Proteins, Signal Transducing; D020816:Amino Acid Motifs; D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D002448:Cell Adhesion; D002455:Cell Division; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement; D050719:Crk-Associated Substrate Protein; D022001:Focal Adhesions; D020662:Guanine Nucleotide Exchange Factors; D015151:Immunoblotting; D051379:Mice; D008809:Mice, Inbred C3H; D008856:Microscopy, Fluorescence; D016297:Mutagenesis, Site-Directed; D010750:Phosphoproteins / Q000378:metabolism*; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000378:metabolism*; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism*; D050717:Retinoblastoma-Like Protein p130; D015398:Signal Transduction; D014162:Transfection; D020827:rap1 GTP-Binding Proteins / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; C493842:Bcar1 protein, mouse; C120867:Bcar3 protein, mouse; D050719:Crk-Associated Substrate Protein; D020662:Guanine Nucleotide Exchange Factors; D010750:Phosphoproteins; D011506:Proteins; D050717:Retinoblastoma-Like Protein p130; D016392:Proto-Oncogene Proteins pp60(c-src); D020827:rap1 GTP-Binding Proteins