Guanine nucleotide-binding protein G

Definition:

Guanine nucleotide-binding proteins (G proteins) function as transducers downstream of G protein-coupled receptors (GPCRs) in numerous signaling cascades. The alpha chain contains the guanine nucleotide binding site and alternates between an active, GTP-bound state and an inactive, GDP-bound state. Signaling by an activated GPCR promotes GDP release and GTP binding. The alpha subunit has a low GTPase activity that converts bound GTP to GDP, thereby terminating the signal. Both GDP release and GTP hydrolysis are modulated by numerous regulatory proteins. Signaling is mediated via effector proteins, such as adenylate cyclase. Inhibits adenylate cyclase activity, leading to decreased intracellular cAMP levels (By similarity). The inactive GDP-bound form prevents the association of RGS14 with centrosomes and is required for the translocation of RGS14 from the cytoplasm to the plasma membrane. Required for normal cytokinesis during mitosis. Required for cortical dynein-dynactin complex recruitment during metaphase.

References:

[1]. Susanne Thiele, et al. Functional characterization of GNAS mutations found in patients with pseudohypoparathyroidism type Ic defines a new subgroup of pseudohypoparathyroidism affecting selectively Gsα-receptor interaction. Hum Mutat. 2011 Jun;32(6):653-60. [Content Brief]

[2]. Xiaodong Li, et al. Human receptors for sweet and umami taste. Proc Natl Acad Sci U S A. 2002 Apr 2;99(7):4692-6. [Content Brief]

[3]. T W Hunt, et al. RGS10 is a selective activator of G alpha i GTPase activity. Nature. 1996 Sep 12;383(6596):175-7. [Content Brief]

[4]. R Mattera, et al. Recombinant alpha i-3 subunit of G protein activates Gk-gated K+ channels. J Biol Chem. 1989 Jan 5;264(1):465-71. [Content Brief]

[5]. Xianlong Gao, et al. Conditional stimulation of type V and VI adenylyl cyclases by G protein betagamma subunits. J Biol Chem. 2007 Jan 5;282(1):294-302. [Content Brief]

[6]. Cameron S Brand, et al. Adenylyl Cyclase 5 Regulation by Gβγ Involves Isoform-Specific Use of Multiple Interaction Sites. Mol Pharmacol. 2015 Oct;88(4):758-67. [Content Brief]

[7]. Muhammad Asif Naeem, et al. GNAT1 associated with autosomal recessive congenital stationary night blindness. Invest Ophthalmol Vis Sci. 2012 Mar 13;53(3):1353-61. [Content Brief]

[8]. Hyeung-Jin Jang, et al. Gut-expressed gustducin and taste receptors regulate secretion of glucagon-like peptide-1. Proc Natl Acad Sci U S A. 2007 Sep 18;104(38):15069-74. [Content Brief]

[9]. Adam J Kimple, et al. Structural determinants of G-protein alpha subunit selectivity by regulator of G-protein signaling 2 (RGS2). J Biol Chem. 2009 Jul 17;284(29):19402-11. [Content Brief]

[10]. Tomomi Kiyomitsu, et al. Chromosome- and spindle-pole-derived signals generate an intrinsic code for spindle position and orientation. Nat Cell Biol. 2012 Feb 12;14(3):311-7. [Content Brief]

[11]. Z Farfel, et al. Pseudohypoparathyroidism, a novel mutation in the betagamma-contact region of Gsalpha impairs receptor stimulation. J Biol Chem. 1996 Aug 16;271(33):19653-5. [Content Brief]

[12]. Hyeseon Cho, et al. Localization of Gi alpha proteins in the centrosomes and at the midbody: implication for their role in cell division. J Cell Biol. 2007 Jul 16;178(2):245-55. [Content Brief]

[13]. Manuel F López-Aranda, et al. Role of a Galphai2 protein splice variant in the formation of an intracellular dopamine D2 receptor pool. J Cell Sci. 2007 Jul 1;120(Pt 13):2171-8. [Content Brief]

[14]. Meera Soundararajan, et al. Structural diversity in the RGS domain and its interaction with heterotrimeric G protein alpha-subunits. Proc Natl Acad Sci U S A. 2008 Apr 29;105(17):6457-62. [Content Brief]

[15]. Youngshil Pak, et al. Direct binding of the beta1 adrenergic receptor to the cyclic AMP-dependent guanine nucleotide exchange factor CNrasGEF leads to Ras activation. Mol Cell Biol. 2002 Nov;22(22):7942-52. [Content Brief]

[16]. Elisa Alvarez-Curto, et al. Targeted Elimination of G Proteins and Arrestins Defines Their Specific Contributions to Both Intensity and Duration of G Protein-coupled Receptor Signaling. J Biol Chem. 2016 Dec 30;291(53):27147-27159. [Content Brief]

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