| Structural highlights
Function
[GNAI1_HUMAN] Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. The G(i) proteins are involved in hormonal regulation of adenylate cyclase: they inhibit the cyclase in response to beta-adrenergic stimuli. 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. May play a role in cell division.[1] [2] [RGS14_RAT] Acts as a regulator of G protein signaling (RGS). Modulates G protein alpha subunits nucleotide exchange and hydrolysis activities by functioning either as a GTPase-activating protein (GAP), thereby driving G protein alpha subunits into their inactive GDP-bound form, or as a GDP-dissociation inhibitor (GDI). Confers GDI activity on G(i) alpha subunits GNAI1 and GNAI3, but not G(o) alpha subunit GNAO1 and G(i) alpha subunit GNAI2. Confers GAP activity on G(o) alpha subunit GNAI0 and G(i) alpha subunits GNAI2 and GNAI3. May act as a scaffold integrating G protein and Ras/Raf MAPkinase signaling pathways. Inhibits platelet-derived growth factor (PDGF)-stimulated ERK1/ERK2 phosphorylation; a process depending on its interaction with HRAS1 and that is reversed by G(i) alpha subunit GNAI1. Acts as a positive modulator of microtubule polymerisation and spindle organization through a G(i)-alpha-dependent mechanism. Plays a role in cell division; required for completion of the first mitotic division of the embryo. Involved in visual memory processing capacity; when overexpressed in the V2 secondary visual cortex area. Involved in hippocampal-based learning and memory; acts as a suppressor of synaptic plasticity in CA2 neurons. Required for the nerve growth factor (NGF)-mediated neurite outgrowth. Involved in stress resistance.[3] [4] [5] [6] [7] [8] [9]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Heterotrimeric G-proteins bind to cell-surface receptors and are integral in transmission of signals from outside the cell. Upon activation of the Galpha subunit by binding of GTP, the Galpha and Gbetagamma subunits dissociate and interact with effector proteins for signal transduction. Regulatory proteins with the 19-amino-acid GoLoco motif can bind to Galpha subunits and maintain G-protein subunit dissociation in the absence of Galpha activation. Here we describe the structural determinants of GoLoco activity as revealed by the crystal structure of Galpha(i1) GDP bound to the GoLoco region of the 'regulator of G-protein signalling' protein RGS14. Key contacts are described between the GoLoco motif and Galpha protein, including the extension of GoLoco's highly conserved Asp/Glu-Gln-Arg triad into the nucleotide-binding pocket of Galpha to make direct contact with the GDP alpha- and beta-phosphates. The structural organization of the GoLoco Galpha(i1) complex, when combined with supporting data from domain-swapping experiments, suggests that the Galpha all-helical domain and GoLoco-region carboxy-terminal residues control the specificity of GoLoco Galpha interactions.
Structural determinants for GoLoco-induced inhibition of nucleotide release by Galpha subunits.,Kimple RJ, Kimple ME, Betts L, Sondek J, Siderovski DP Nature. 2002 Apr 25;416(6883):878-81. PMID:11976690[10]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Cho H, Kehrl JH. 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. PMID:17635935 doi:10.1083/jcb.200604114
- ↑ Johnston CA, Siderovski DP. Structural basis for nucleotide exchange on G alpha i subunits and receptor coupling specificity. Proc Natl Acad Sci U S A. 2007 Feb 6;104(6):2001-6. Epub 2007 Jan 30. PMID:17264214
- ↑ Kimple RJ, De Vries L, Tronchere H, Behe CI, Morris RA, Gist Farquhar M, Siderovski DP. RGS12 and RGS14 GoLoco motifs are G alpha(i) interaction sites with guanine nucleotide dissociation inhibitor Activity. J Biol Chem. 2001 Aug 3;276(31):29275-81. Epub 2001 May 31. PMID:11387333 doi:http://dx.doi.org/10.1074/jbc.M103208200
- ↑ Mittal V, Linder ME. The RGS14 GoLoco domain discriminates among Galphai isoforms. J Biol Chem. 2004 Nov 5;279(45):46772-8. Epub 2004 Aug 26. PMID:15337739 doi:http://dx.doi.org/10.1074/jbc.M407409200
- ↑ Willard FS, Willard MD, Kimple AJ, Soundararajan M, Oestreich EA, Li X, Sowa NA, Kimple RJ, Doyle DA, Der CJ, Zylka MJ, Snider WD, Siderovski DP. Regulator of G-protein signaling 14 (RGS14) is a selective H-Ras effector. PLoS One. 2009;4(3):e4884. doi: 10.1371/journal.pone.0004884. Epub 2009 Mar 25. PMID:19319189 doi:http://dx.doi.org/10.1371/journal.pone.0004884
- ↑ Lopez-Aranda MF, Lopez-Tellez JF, Navarro-Lobato I, Masmudi-Martin M, Gutierrez A, Khan ZU. Role of layer 6 of V2 visual cortex in object-recognition memory. Science. 2009 Jul 3;325(5936):87-9. doi: 10.1126/science.1170869. PMID:19574389 doi:http://dx.doi.org/10.1126/science.1170869
- ↑ Shu FJ, Ramineni S, Hepler JR. RGS14 is a multifunctional scaffold that integrates G protein and Ras/Raf MAPkinase signalling pathways. Cell Signal. 2010 Mar;22(3):366-76. doi: 10.1016/j.cellsig.2009.10.005. Epub . PMID:19878719 doi:http://dx.doi.org/10.1016/j.cellsig.2009.10.005
- ↑ Lin YR, Kim K, Yang Y, Ivessa A, Sadoshima J, Park Y. Regulation of longevity by regulator of G-protein signaling protein, Loco. Aging Cell. 2011 Jun;10(3):438-47. doi: 10.1111/j.1474-9726.2011.00678.x. Epub, 2011 Mar 22. PMID:21255223 doi:http://dx.doi.org/10.1111/j.1474-9726.2011.00678.x
- ↑ Vellano CP, Shu FJ, Ramineni S, Yates CK, Tall GG, Hepler JR. Activation of the regulator of G protein signaling 14-Galphai1-GDP signaling complex is regulated by resistance to inhibitors of cholinesterase-8A. Biochemistry. 2011 Feb 8;50(5):752-62. doi: 10.1021/bi101910n. Epub 2011 Jan 11. PMID:21158412 doi:http://dx.doi.org/10.1021/bi101910n
- ↑ Kimple RJ, Kimple ME, Betts L, Sondek J, Siderovski DP. Structural determinants for GoLoco-induced inhibition of nucleotide release by Galpha subunits. Nature. 2002 Apr 25;416(6883):878-81. PMID:11976690 doi:http://dx.doi.org/10.1038/416878a
|
