title: Dissociation of focal adhesion kinase and paxillin tyrosine phosphorylation induced by bombesin and lysophosphatidic acid from epidermal growth factor receptor transactivation in Swiss 3T3 cells.
abstract: Tyrosine phosphorylation of the nonreceptor tyrosine kinase p125 focal adhesion kinase (FAK) and the adapter protein paxillin is rapidly increased by multiple agonists, including bombesin (BOM) and lysophosphatidic acid (LPA), through heptahelical G protein-coupled receptors (GPCRs). The pathways involved remain incompletely understood. The experiments presented here were designed to test the role of epidermal growth factor receptor (EGFR) transactivation in the rapid increase of tyrosine phosphorylation of FAK and paxillin induced by GPCR agonists. Our results show that treatment with the selective EGFR tyrosine kinase inhibitor AG 1478, at concentrations that completely blocked the increase in tyrosine phosphorylation of these proteins induced by EGF, did not affect the stimulation of tyrosine phosphorylation of either FAK or paxillin induced by multiple GPCR agonists including LPA, BOM, vasopressin, bradykinin, and endothelin. Similar results were obtained when Swiss 3T3 cells were treated with another highly specific inhibitor of the EGF receptor kinase activity, PD-158780. Collectively, our results clearly dissociate EGFR transactivation from the tyrosine phosphorylation of FAK and paxillin induced by multiple GPCR agonists.
authors.affiliation: Department of Medicine, School of Medicine and Molecular Biology Institute, University of California, Los Angeles, California 90095-178622, USA.
authors.forename: Eduardo Perez
authors.initials: EP
authors.lastname: Salazar
authors.forename: Isabel
authors.initials: I
authors.lastname: Hunger-Glaser
authors.forename: Enrique
authors.initials: E
authors.lastname: Rozengurt
mesh_terms: D016475:3T3 Cells; D000818:Animals; D001839:Bombesin / Q000494:pharmacology*; D001920:Bradykinin / Q000494:pharmacology; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D016232:Endothelins / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism*; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D019204:GTP-Binding Proteins / Q000378:metabolism; D008246:Lysophospholipids / Q000494:pharmacology*; D051379:Mice; D051419:Paxillin; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011743:Pyrimidines / Q000494:pharmacology; D011799:Quinazolines; D022502:Stress Fibers / Q000187:drug effects; D014443:Tyrosine / Q000378:metabolism; D020032:Tyrphostins / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014667:Vasopressins / Q000494:pharmacology
chemical_list: C107875:6-(methylamino)pyrido(3,4-d)pyrimidine; D003598:Cytoskeletal Proteins; D016232:Endothelins; D004791:Enzyme Inhibitors; D008246:Lysophospholipids; D051419:Paxillin; D010750:Phosphoproteins; C496062:Pxn protein, mouse; D011743:Pyrimidines; D011799:Quinazolines; D020032:Tyrphostins; D014662:Vasoconstrictor Agents; D014667:Vasopressins; C101044:RTKI cpd; D014443:Tyrosine; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496051:Ptk2 protein, mouse; D019204:GTP-Binding Proteins; D001839:Bombesin; D001920:Bradykinin