Tyrosine phosphorylation of p130(cas) by bombesin, lysophosphatidic acid, phorbol esters, and platelet-derived growth factor. Signaling pathways and formation of a p130(cas)-Crk complex.
Treatment of Swiss 3T3 cells with bombesin rapidly induced tyrosine phosphorylation of the p130 Crk-associated substrate (p130(cas)). Vasopressin, endothelin, bradykinin, lysophosphatidic acid, sphingosylphosphorylcholine, and phorbol 12,13-dibutyrate also stimulated p130(cas) tyrosine phosphorylation. Bombesin-induced p130(cas) tyrosine phosphorylation could be dissociated from both protein kinase C activation and Ca2+ mobilization from intracellular stores. In contrast, cytochalasin D, which disrupts the network of actin microfilaments, completely prevented tyrosine phosphorylation of p130(cas) by bombesin. Platelet-derived growth factor, at low concentrations (1-5 ng/ml), also induced tyrosine phosphorylation of p130(cas) via a pathway that depended on the integrity of the actin cytoskeleton. The phosphatidylinositol 3'-kinase inhibitors wortmannin and LY294002 prevented tyrosine phosphorylation of p130(cas) in response to platelet-derived growth factor but not in response to neuropeptides, lysophosphatidic acid, sphingosylphosphorylcholine, or phorbol 12,13-dibutyrate. All agonists that induced p130(cas) tyrosine phosphorylation also promoted the formation of a p130(cas).Crk complex in intact Swiss 3T3 cells. Thus, our results identified distinct signal transduction pathways that lead to tyrosine phosphorylation of p130(cas) in the same cells and suggest that p130(cas) could play a role in mitogen-mediated signal transduction.
Casamassima
A
A
Imperial Cancer Research Fund, P. O. Box 123, 44 Lincoln's Inn Fields, London WC2A 3PX, United Kingdom.
Rozengurt
E
E
D016475:3T3 Cells; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D001839:Bombesin / Q000378:metabolism*; D001920:Bradykinin / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002867:Chromones / Q000494:pharmacology; D050719:Crk-Associated Substrate Protein; D016232:Endothelins / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008246:Lysophospholipids / Q000378:metabolism*; D051379:Mice; D009025:Morpholines / Q000494:pharmacology; D010703:Phorbol Esters / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D011506:Proteins; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D050721:Proto-Oncogene Proteins c-cbl; D016160:Retinoblastoma Protein / Q000378:metabolism*; D050717:Retinoblastoma-Like Protein p130; D014443:Tyrosine / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases; D014667:Vasopressins / Q000378:metabolism; D000077191:Wortmannin
D000730:Androstadienes; C493842:Bcar1 protein, mouse; D002867:Chromones; D050719:Crk-Associated Substrate Protein; D016232:Endothelins; D004791:Enzyme Inhibitors; D008246:Lysophospholipids; D009025:Morpholines; D010703:Phorbol Esters; D010750:Phosphoproteins; D010982:Platelet-Derived Growth Factor; D011506:Proteins; D011518:Proto-Oncogene Proteins; D016160:Retinoblastoma Protein; D050717:Retinoblastoma-Like Protein p130; D014667:Vasopressins; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D014443:Tyrosine; D050721:Proto-Oncogene Proteins c-cbl; D044767:Ubiquitin-Protein Ligases; D011493:Protein Kinase C; C067419:CBL protein, human; C493849:Cbl protein, mouse; D001839:Bombesin; D001920:Bradykinin; D002118:Calcium; D000077191:Wortmannin