G protein activation of a hormone-stimulated phosphatase in human tumor cells.
The growth-inhibiting peptide hormone somatostatin stimulates phosphotyrosine phosphatase activity in the human pancreatic cell line MIA PaCa-2. This hormonal activation was mediated by a pertussis toxin-sensitive guanosine 5'-triphosphate-binding protein (G protein) in the membranes of these cells. Activation of this G protein by somatostatin stimulated the dephosphorylation of exogenous epidermal growth factor receptor prepared from A-431 cells in vitro. This pathway may mediate the antineoplastic action of somatostatin in these cells and in human tumors and could represent a general mechanism of G protein coupling that is utilized by normal cells in the hormonal control of cell growth.
Vollum Institute for Advanced Biomedical Research, Oregon Health Sciences University, Portland 97201.
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Florio
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Stork
D000255:Adenosine Triphosphate / Q000378:metabolism; D002294:Carcinoma, Squamous Cell; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D066246:ErbB Receptors / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006153:Guanosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D010190:Pancreatic Neoplasms; D010455:Peptides / Q000378:metabolism; D037342:Pertussis Toxin; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D013004:Somatostatin / Q000494:pharmacology*; D013873:Thionucleotides / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D010455:Peptides; D013873:Thionucleotides; D010566:Virulence Factors, Bordetella; D006153:Guanosine Diphosphate; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D013004:Somatostatin; C023427:guanosine 5'-O-(2-thiodiphosphate); D000255:Adenosine Triphosphate; D037342:Pertussis Toxin; D011494:Protein Kinases; D066246:ErbB Receptors; D017027:Protein Tyrosine Phosphatases; D019204:GTP-Binding Proteins