Abstract
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.
MeSH terms
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Adenosine Triphosphate / metabolism
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Carcinoma, Squamous Cell
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Cell Line
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Cell Membrane / metabolism
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Dose-Response Relationship, Drug
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Enzyme Activation
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ErbB Receptors / metabolism
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GTP-Binding Proteins / metabolism*
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Guanosine 5'-O-(3-Thiotriphosphate) / pharmacology
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Guanosine Diphosphate / analogs & derivatives
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Guanosine Diphosphate / pharmacology
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Humans
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Kinetics
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Pancreatic Neoplasms
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Peptides / metabolism
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Pertussis Toxin
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Phosphorylation
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Protein Kinases / metabolism
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Protein Tyrosine Phosphatases / metabolism*
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Somatostatin / pharmacology*
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Thionucleotides / pharmacology
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Virulence Factors, Bordetella / pharmacology
Substances
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Peptides
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Thionucleotides
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Virulence Factors, Bordetella
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Guanosine Diphosphate
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Guanosine 5'-O-(3-Thiotriphosphate)
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Somatostatin
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guanosine 5'-O-(2-thiodiphosphate)
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Adenosine Triphosphate
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Pertussis Toxin
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Protein Kinases
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ErbB Receptors
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Protein Tyrosine Phosphatases
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GTP-Binding Proteins