RGS4和GAIP是Gqα的GTP酶激活蛋白，可通过γ-硫代-GTP-Gqα阻断磷脂酶Cβ的激活。
RGS4 and GAIP are GTPase-activating proteins for Gq alpha and block activation of phospholipase C beta by gamma-thio-GTP-Gq alpha.
作者信息
Hepler J R, Berman D M, Gilman A G, Kozasa T
机构信息
Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas 75235-9041, USA.
出版信息
Proc Natl Acad Sci U S A. 1997 Jan 21;94(2):428-32. doi: 10.1073/pnas.94.2.428.
Abstract
RGS proteins constitute a newly appreciated and large group of negative regulators of G protein signaling. Four members of the RGS family act as GTPase-activating proteins (GAPs) with apparent specificity for members of the Gi alpha subfamily of G protein subunits. We demonstrate here that two RGS proteins, RGS4 and GAIP, also act as GAPs for Gq alpha, the G alpha protein responsible for activation of phospholipase C beta. Furthermore, these RGS proteins block activation of phospholipase C beta by guanosine 5'-(3-O-thio) triphosphate-Gq alpha. GAP activity does not explain this effect, which apparently results from occlusion of the binding site on G alpha for effector. Inhibitory effects of RGS proteins on G protein-mediated signaling pathways can be demonstrated by simple mixture of RGS4 or GAIP with plasma membranes.
摘要
RGS蛋白构成了一类新近受到重视的、对G蛋白信号传导起负调节作用的大家族。RGS家族的四个成员作为GTP酶激活蛋白（GAP），对G蛋白亚基Giα亚家族的成员具有明显的特异性。我们在此证明，两种RGS蛋白，即RGS4和GAIP，也可作为Gqα的GAP，Gqα是负责激活磷脂酶Cβ的Gα蛋白。此外，这些RGS蛋白可通过鸟苷5'-（3-O-硫代）三磷酸-Gqα阻断磷脂酶Cβ的激活。GAP活性并不能解释这种效应，这种效应显然是由于效应器对Gα上结合位点的封闭所致。通过将RGS4或GAIP与质膜简单混合，即可证明RGS蛋白对G蛋白介导的信号通路具有抑制作用。
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本文引用的文献
1
RGS proteins and signaling by heterotrimeric G proteins.RGS蛋白与异源三聚体G蛋白信号传导
J Biol Chem. 1997 Feb 14;272(7):3871-4. doi: 10.1074/jbc.272.7.3871.
2
GAIP is membrane-anchored by palmitoylation and interacts with the activated (GTP-bound) form of G alpha i subunits.GAIP 通过棕榈酰化作用锚定在膜上，并与 Gαi 亚基的活化（GTP 结合）形式相互作用。
Proc Natl Acad Sci U S A. 1996 Dec 24;93(26):15203-8. doi: 10.1073/pnas.93.26.15203.
3
The GTPase-activating protein RGS4 stabilizes the transition state for nucleotide hydrolysis.GTP酶激活蛋白RGS4稳定核苷酸水解的过渡态。
J Biol Chem. 1996 Nov 1;271(44):27209-12. doi: 10.1074/jbc.271.44.27209.
4
RGS10 is a selective activator of G alpha i GTPase activity.RGS10是Gαi GTP酶活性的选择性激活剂。
Nature. 1996 Sep 12;383(6596):175-7. doi: 10.1038/383175a0.
5
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6
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7
A new family of regulators of G-protein-coupled receptors?G蛋白偶联受体的新型调节因子家族？
Curr Biol. 1996 Feb 1;6(2):211-2. doi: 10.1016/s0960-9822(02)00454-2.
8
Regulation of phospholipase C-beta1 by Gq and m1 muscarinic cholinergic receptor. Steady-state balance of receptor-mediated activation and GTPase-activating protein-promoted deactivation.Gq和M1毒蕈碱胆碱能受体对磷脂酶C-β1的调节。受体介导的激活与GTP酶激活蛋白促进的失活之间的稳态平衡。
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9
Inhibition of G-protein-mediated MAP kinase activation by a new mammalian gene family.一个新的哺乳动物基因家族对G蛋白介导的丝裂原活化蛋白激酶激活的抑制作用。
Nature. 1996 Feb 22;379(6567):742-6. doi: 10.1038/379742a0.
10
Functional importance of the amino terminus of Gq alpha.Gqα氨基末端的功能重要性。
J Biol Chem. 1996 Jan 5;271(1):496-504. doi: 10.1074/jbc.271.1.496.
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