title: Adhesion through the interaction of lymphocyte function-associated antigen-1 with intracellular adhesion molecule-1 induces tyrosine phosphorylation of p130cas and its association with c-CrkII.
abstract: The B-lymphoblastoid cell line JY undergoes homotypic aggregation in a lymphocyte function-associated antigen-1 (LFA-1)-mediated, intracellular adhesion molecule-1 (ICAM-1)-dependent manner when stimulated with phorbol 12-myristate 13-acetate or anti-LFA-1 antibodies. Under conditions that lead to cell aggregation, we observed rapid tyrosine phosphorylation of p130cas, a protein previously identified to be phosphorylated on tyrosine in both v-src- and v-crk-transformed cells. Phosphorylation of p130cas was dependent on binding of LFA-1 to its ligand, ICAM-1, as demonstrated by the use of anti-ICAM-1 antibodies. Several observations suggest that this event may be an important step in the signaling pathway initiated by LFA-1. p130cas phosphorylation was rapidly reversible upon disengagement of the LFA-1-ICAM-1 complex and required cell adhesion since binding of phorbol 12-myristate 13-acetate-stimulated JY cells to purified ICAM-1 or cross-linking of either LFA-1 or ICAM-1 was not sufficient to induce phosphorylation of p130cas. The integrin-stimulated phosphorylation of p130cas created binding sites that were recognized in vitro by the SH2 domain of c-CrkII, a key adaptor protein involved in cell differentiation and transformation. Moreover, we also showed that the LFA-1-stimulated tyrosine phosphorylation of p130cas induces the formation of a p130cas.CrkII and p130cas.CrkL complex in intact cells. This observation suggests that adhesion mediated by the interaction of LFA-1 and ICAM-1 initiates a signaling cascade that involves the activation of protein tyrosine kinases and leads to the regulation of protein-protein interaction via SH2 domains, a key process shared with growth factor signaling pathways.
authors.affiliation: Department of Internal medicine, University of Michigan, Ann Arbor, 48109-0668, USA.
authors.forename: L
authors.initials: L
authors.lastname: Petruzzelli
authors.forename: M
authors.initials: M
authors.lastname: Takami
authors.forename: R
authors.initials: R
authors.lastname: Herrera
mesh_terms: D000906:Antibodies / Q000494:pharmacology; D001402:B-Lymphocytes; D002448:Cell Adhesion; D002449:Cell Aggregation; D002460:Cell Line; D050719:Crk-Associated Substrate Protein; D003432:Cross-Linking Reagents; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology / Q000502:physiology*; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology*; D010750:Phosphoproteins / Q000302:isolation & purification / Q000378:metabolism*; D010766:Phosphorylation; D019000:Phosphotyrosine; D011494:Protein Kinases / Q000302:isolation & purification / Q000378:metabolism*; D011506:Proteins; D011518:Proto-Oncogene Proteins; D050737:Proto-Oncogene Proteins c-crk; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000378:metabolism; D050717:Retinoblastoma-Like Protein p130; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D000906:Antibodies; C493841:BCAR1 protein, human; D050719:Crk-Associated Substrate Protein; D003432:Cross-Linking Reagents; D016169:Lymphocyte Function-Associated Antigen-1; D010750:Phosphoproteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D050737:Proto-Oncogene Proteins c-crk; D011993:Recombinant Fusion Proteins; D016160:Retinoblastoma Protein; D050717:Retinoblastoma-Like Protein p130; D018799:Intercellular Adhesion Molecule-1; D019000:Phosphotyrosine; D005982:Glutathione Transferase; D011494:Protein Kinases; D013755:Tetradecanoylphorbol Acetate