A C-terminal mutant of the G protein beta subunit deficient in the activation of phospholipase C-beta

作者：Zhang SY; Coso OA; Collins R; Gutkind JS; Simonds WF

来源：Journal of Biological Chemistry, 1996, 271(33): 20208-20212.

The molecular mechanism by which the G protein py complex modulates multiple mammalian effector pathways is unknown. Homolog-scanning mutagenesis of the G protein beta subunit was employed to identify residues critical for the activation of phospholipase C-beta(2) (PLC-beta(2)). A series of chimeras was made by introducing small segments of the Dictyostelium beta subunit into a background of mammalian beta(1) and tested in COS cell cotransfection assays for their ability ito activate PLC-beta(2), and assemble with mammalian gamma(2). A chimera that contained four Dictyostelium beta substitutions within the C-terminal 14 residues was unable to activate PLC beta(2), when cotransfected with gamma, despite its demonstrable expression in a gamma-dependent manner. Cotransfection of the mutant blocked m2 muscarinic receptor activation of PLC by a pertussis toxin-sensitive pathway. This C-terminal mutant retained the ability, however, to stimulate the mitogen-activated protein kinase pathway. These results imply that activation of different beta gamma-responsive effectors is mediated by distinct domains.

• 出版日期1996-8-16