Analysis of the Gs/mitogen-activated protein kinase pathway in mutant S49 cells.
Heterotrimeric G protein-coupled receptors can activate the mitogen-activated protein kinase (MAPK) cascade. Recent studies using pharmacological inhibitors or dominant-negative mutants of signaling molecules have advanced our understanding of the pathways from G protein-coupled receptors to MAPK. However, molecular genetic analysis of these pathways is inadequate in mammalian cells. Here, using the well characterized Gsalpha- and protein kinase A-deficient S49 mouse lymphoma cells, we provide the molecular genetic evidence that Gsalpha is responsible for transducing the beta-adrenergic receptor signal to MAPK in a protein kinase A-dependent pathway involving Rap1 and Raf (but not Ras) molecules.
Wan
Y
Y
Department of Physiology, Cornell University Medical College, New York, New York 10021, USA.
Huang
X Y
XY
D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000172:deficiency / Q000502:physiology; D004789:Enzyme Activation / Q000502:physiology; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000502:physiology; D008223:Lymphoma / Q000378:metabolism; D051379:Mice; D011487:Protein Conformation; D019908:Proto-Oncogene Proteins c-raf / Q000502:physiology; D015800:Protozoan Proteins / Q000502:physiology; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics*; D014407:Tumor Cells, Cultured; D018631:ras Proteins / Q000502:physiology
D015800:Protozoan Proteins; D011943:Receptors, Adrenergic, beta; C065352:rhoptry associated protein, Plasmodium; D019908:Proto-Oncogene Proteins c-raf; D017868:Cyclic AMP-Dependent Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019204:GTP-Binding Proteins; D019205:GTP-Binding Protein alpha Subunits, Gs; D018631:ras Proteins