A Region of Adenylyl Cyclase 2 Critical for Regulation by G Protein βγ Subunits

作者：Jianqiang Chen, Michael J. DeVivo, Jane Dingus, Anya Harry, Jingrong Li, Jinliang Sui, Donna J. Carty, Jonathan L. Blank, John H. Exton, Robert H. Stoffel, James Inglese, Robert J. Lefkowitz, Diomedes E. Logothetis, John D. Hildebrandt, Ravi lyengar · 发表于：Science · 年份：1995 · DOI：10.1126/science.7761832 · 被引用次数：280 · 研究领域：Receptor Mechanisms and Signaling、Protein Kinase Regulation and GTPase Signaling、Ion channel regulation and function

Receptor-mediated activation of heterotrimeric guanine nucleotide-binding proteins (G proteins) results in the dissociation of alpha from beta gamma subunits, thereby allowing both to regulate effectors. Little is known about the regions of effectors required for recognition of G beta gamma. A peptide encoding residues 956 to 982 of adenylyl cyclase 2 specifically blocked G beta gamma stimulation of adenylyl cyclase 2, phospholipase C-beta 3, potassium channels, and beta-adrenergic receptor kinase as well as inhibition of calmodulin-stimulated adenylyl cyclases, but had no effect on interactions between G beta gamma and G alpha o. Substitutions in this peptide identified a functionally important motif, Gln-X-X-Glu-Arg, that is also conserved in regions of potassium channels and beta-adrenergic receptor kinases that participate in G beta gamma interactions. Thus, the region defined by residues 956 to 982 of adenylyl cyclase 2 may contain determinants important for receiving signals from G beta gamma.