title: Gialpha but not gqalpha is linked to activation of p21(ras) in human airway smooth muscle cells.
abstract: Airway smooth muscle hypertrophy contributes to the narrowing of asthmatic airways. Activation of the mitogen-activated protein kinases is an important event in mediating cell proliferation. Because the monomeric G protein p21(ras) is an important intermediate leading to activation of mitogen-activated protein kinases, we questioned which heterotrimeric G protein-coupled receptors were linked to the activation of p21(ras) in cultured human airway smooth muscle and which of the heterotrimeric G protein subunits (alpha or betagamma) transmitted the activation signal. Carbachol and endothelin-1 increased GTP-bound p21(ras) in a pertussis toxin-sensitive manner [ratio of [32P]GTP to ([32P]GTP + [32P]GDP): control, 30 +/- 1.7; 3 min of 1 microM carbachol, 39 +/- 1.1; 3 min of 1 microM endothelin-1, 40 +/- 1.2], whereas histamine, bradykinin, and KCl were without effect. Transfection of an inhibitor of the G protein betagamma-subunit [the carboxy terminus (Gly495-Leu689) of the beta-adrenoceptor kinase 1] failed to inhibit the carbachol-induced activation of p21(ras). These data suggest that Gi- but not Gq-coupled receptors activate p21(ras) in human airway smooth muscle cells, and this effect most likely involves the alpha-subunit.
authors: Department of Anesthesiology, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
authors: C W
authors: CW
authors: Emala
authors: F
authors: F
authors: Liu
authors: C A
authors: CA
authors: Hirshman
mesh_terms: D001920:Bradykinin / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism; D019332:Endothelin-1 / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D006153:Guanosine Diphosphate / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism; D037342:Pertussis Toxin; D011189:Potassium Chloride / Q000494:pharmacology; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D014132:Trachea / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D014162:Transfection; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D019332:Endothelin-1; D010446:Peptide Fragments; D011994:Recombinant Proteins; D010566:Virulence Factors, Bordetella; D006153:Guanosine Diphosphate; D011189:Potassium Chloride; D006632:Histamine; D006160:Guanosine Triphosphate; D002217:Carbachol; D037342:Pertussis Toxin; D017868:Cyclic AMP-Dependent Protein Kinases; C114043:BARKct protein, recombinant; D019204:GTP-Binding Proteins; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras); D001920:Bradykinin