Analysis of the G(s)/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 G(s)(α-) and protein kinase A-deficient S49 mouse lymphoma cells, we provide the molecular genetic evidence that G(s)α is responsible for transducing the β-adrenergic receptor signal to MAPK in a protein kinase A-dependent pathway involving Rap1 and Raf (but not Ras) molecules.