Tyrosine phosphorylation of p130Cas and cortactin accompanies integrin-mediated cell adhesion to extracellular matrix.
We show in this report that two v-src substrate proteins, p130Cas and cortactin, become tyrosine-phosphorylated during integrin-mediated cell adhesion to extracellular matrix substrata and upon cell attachment onto immobilized anti-integrin antibodies. This tyrosine phosphorylation does not occur when cells attach to polylysine or through antibodies against major histocompatibility complex. It also does not take place when adhesion-mediated reorganization of the actin cytoskeleton is inhibited with cytochalasin D. Tyrosine phosphorylation of p130Cas and cortactin coincides with tyrosine phosphorylation of focal adhesion kinase during integrin-mediated cell adhesion but is independent of cell adhesion in v-src-transformed cells. The tyrosine-phosphorylated sites in p130Cas and cortactin may serve as binding sites for proteins containing Src homology 2 domains, as is the case with two other integrin-regulated docking proteins, focal adhesion kinase and paxillin. Thus, these results suggest that ligand binding of integrins regulates the tyrosine phosphorylation state of multiple docking proteins. These proteins may mediate anchorage dependence of growth; their misregulation in v-src-transformed and other tumorigenic cells may be responsible for the anchorage independence of such cells.
Vuori
K
K
Cancer Research Center, La Jolla Cancer Research Foundation, California 92037, USA.
Ruoslahti
E
E
D016475:3T3 Cells; D008841:Actin Cytoskeleton / Q000648:ultrastructure; D000199:Actins / Q000378:metabolism; D000818:Animals; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D002478:Cells, Cultured; D051356:Cortactin; D050719:Crk-Associated Substrate Protein; D005109:Extracellular Matrix / Q000378:metabolism*; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D016391:Genes, src; D066298:In Vitro Techniques; D016023:Integrins / Q000378:metabolism*; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011506:Proteins; D051381:Rats; D050717:Retinoblastoma-Like Protein p130; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D000199:Actins; C493842:Bcar1 protein, mouse; C493843:Bcar1 protein, rat; D015815:Cell Adhesion Molecules; D051356:Cortactin; D050719:Crk-Associated Substrate Protein; C495869:Cttn protein, mouse; C495870:Cttn protein, rat; D016023:Integrins; D008840:Microfilament Proteins; D010750:Phosphoproteins; D011506:Proteins; D050717:Retinoblastoma-Like Protein p130; D019000:Phosphotyrosine; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496051:Ptk2 protein, mouse; C496052:Ptk2 protein, rat