Activation of transforming G protein-coupled receptors induces rapid tyrosine phosphorylation of cellular proteins, including p125FAK and the p130 v-src substrate.
We have used the family of human muscarinic receptors (mAChRs) as a model for receptors coupled to G proteins and have shown that genes for certain mAChR subtypes can behave as potent agonist-dependent oncogenes. Furthermore, transforming mAChRs can transduce mitogenic signals in transfected NIH 3T3 cells. In this study, we show that in cells expressing ml mAChRs, the cholinergic agonist carbachol, induces a rapid and dose-dependent increase in tyrosine phosphorylation of cellular proteins which are different from those induced by PDGF. Interestingly, carbachol, but not PDGF, induces an increase in tyrosine phosphorylation of the p125FAK and p130 v-src substrates. Thus, growth promoting pathways activated by receptors coupled to G proteins might involve tyrosine phosphorylation of a small set of cellular proteins previously identified as substrates for oncogene-encoded tyrosine kinases.
Gutkind
J S
JS
Laboratory of Cellular Development and Oncology, National Institute of Dental Research, NIH, Bethesda, Maryland 20892.
Robbins
K C
KC
D019870:1-Phosphatidylinositol 4-Kinase; D016475:3T3 Cells; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D019204:GTP-Binding Proteins / Q000378:metabolism*; D016391:Genes, src; D006801:Humans; D051379:Mice; D010766:Phosphorylation; D010770:Phosphotransferases / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism*; D012191:Retroviridae Proteins / Q000378:metabolism*; D015398:Signal Transduction; D014162:Transfection; D014443:Tyrosine
D015815:Cell Adhesion Molecules; D010982:Platelet-Derived Growth Factor; D011976:Receptors, Muscarinic; D012191:Retroviridae Proteins; D014443:Tyrosine; D002217:Carbachol; D010770:Phosphotransferases; D019870:1-Phosphatidylinositol 4-Kinase; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human; C496051:Ptk2 protein, mouse; D019204:GTP-Binding Proteins