For example, although most of the actions of the prototype 2 -adrenergic receptor are mediated through G s proteins and the cyclic-AMP-dependent protein kinase PKA system 5, 6-adrenergic receptors can also couple to G i proteins 1, 2. Here we investigate the mechanism that cyyclase the specificity of this coupling. We show that in HEK cells, stimulation of mitogen-activated protein MAP kinase by the 2 -adrenergic receptor is addenylyl by the subunits of pertussis-toxin-sensitive G proteins through a pathway involving the non-receptor tyrosine kinase c-Src and the G protein Ras.
Activation of this forskolin-stimulated adenylyl cyclase activity by the 2 -adrenergic receptor requires that the receptor be phosphorylated by PKA because it is blocked by H, an adenylul of PKA. Additionally, a mutant of the receptor, which lacks the sites normally phosphorylated by PKA, can activate adenylyl cyclase 5the enzyme that forskolin-sstimulated cAMP, but not MAP kinase.
Our results demonstrate that a mechanism previously shown to mediate uncoupling of the 2 -adrenergic receptor from G s and thus heterologous desensitization 7 PKA-mediated receptor phosphorylationalso serves to 'switch' coupling of this receptor from G s to G i and initiate a new set of signalling events. To read this story in full you will need to login or make a payment see right.
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Send to a friend. Export citation Export forskolin-stimulated adenylyl cyclase activity Rights and permissions Order commercial reprints. Search Pubmed for Yehia Daaka Louis M. Faculty Position for Research Director of the Animal BSL3 Facility at Duke-NUS. Program and Integrated MS-Ph. Program of IBS School-UST.
Institute for Basic Science. More science jobs Switching of the coupling of the 2 -adrenergic receptor to different G proteins by protein kinase A Yehia Daaka 1. Howard Hughes Medical Institute, Departments of Medicine and Biochemistry, BoxDuke University Medical Center, Durham, North CarolinaUSA Correspondence to: Robert J.