7ydj

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]} GNA12_HUMAN Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems (PubMed:12515866, PubMed:15240885, PubMed:15525651, PubMed:16705036, PubMed:16787920, PubMed:17565996, PubMed:22609986, PubMed:23762476, PubMed:27084452). Activates effector molecule RhoA by binding and activating RhoGEFs (ARHGEF12/LARG) (PubMed:12515866, PubMed:15240885, PubMed:16202387). GNA12-dependent Rho signaling subsequently regulates transcription factor AP-1 (activating protein-1) (By similarity). GNA12-dependent Rho signaling also regulates protein phosphatese 2A activation causing dephosphorylation of its target proteins (PubMed:15525651, PubMed:17565996). Promotes tumor cell invasion and metastasis by activating RhoA/ROCK signaling pathway and up-regulating pro-inflammatory cytokine production (PubMed:16705036, PubMed:16787920, PubMed:23762476, PubMed:27084452). Inhibits CDH1-mediated cell adhesion in process independent from Rho activation (PubMed:11976333, PubMed:16787920). Together with NAPA promotes CDH5 localization to plasma membrane (PubMed:15980433). May play a role in the control of cell migration through the TOR signaling cascade (PubMed:22609986).[UniProtKB:P27600]^{[3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13]}

See Also

• Transducin 3D structures

References

1. ↑ 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
2. ↑ 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
3. ↑ Meigs TE, Fedor-Chaiken M, Kaplan DD, Brackenbury R, Casey PJ. Galpha12 and Galpha13 negatively regulate the adhesive functions of cadherin. J Biol Chem. 2002 Jul 5;277(27):24594-600. PMID:11976333 doi:10.1074/jbc.M201984200
4. ↑ Suzuki N, Nakamura S, Mano H, Kozasa T. Galpha 12 activates Rho GTPase through tyrosine-phosphorylated leukemia-associated RhoGEF. Proc Natl Acad Sci U S A. 2003 Jan 21;100(2):733-8. PMID:12515866 doi:10.1073/pnas.0234057100
5. ↑ Krakstad BF, Ardawatia VV, Aragay AM. A role for Galpha12/Galpha13 in p120ctn regulation. Proc Natl Acad Sci U S A. 2004 Jul 13;101(28):10314-9. PMID:15240885 doi:10.1073/pnas.0401366101
6. ↑ Zhu D, Kosik KS, Meigs TE, Yanamadala V, Denker BM. Galpha12 directly interacts with PP2A: evidence FOR Galpha12-stimulated PP2A phosphatase activity and dephosphorylation of microtubule-associated protein, tau. J Biol Chem. 2004 Dec 31;279(53):54983-6. PMID:15525651 doi:10.1074/jbc.C400508200
7. ↑ Andreeva AV, Kutuzov MA, Vaiskunaite R, Profirovic J, Meigs TE, Predescu S, Malik AB, Voyno-Yasenetskaya T. G alpha12 interaction with alphaSNAP induces VE-cadherin localization at endothelial junctions and regulates barrier function. J Biol Chem. 2005 Aug 26;280(34):30376-83. PMID:15980433 doi:10.1074/jbc.M502844200
8. ↑ Kelly P, Moeller BJ, Juneja J, Booden MA, Der CJ, Daaka Y, Dewhirst MW, Fields TA, Casey PJ. The G12 family of heterotrimeric G proteins promotes breast cancer invasion and metastasis. Proc Natl Acad Sci U S A. 2006 May 23;103(21):8173-8. PMID:16705036 doi:10.1073/pnas.0510254103
9. ↑ Kelly P, Stemmle LN, Madden JF, Fields TA, Daaka Y, Casey PJ. A role for the G12 family of heterotrimeric G proteins in prostate cancer invasion. J Biol Chem. 2006 Sep 8;281(36):26483-90. PMID:16787920 doi:10.1074/jbc.M604376200
10. ↑ Yanamadala V, Negoro H, Gunaratnam L, Kong T, Denker BM. Galpha12 stimulates apoptosis in epithelial cells through JNK1-mediated Bcl-2 degradation and up-regulation of IkappaBalpha. J Biol Chem. 2007 Aug 17;282(33):24352-63. PMID:17565996 doi:10.1074/jbc.M702804200
11. ↑ Gan X, Wang J, Wang C, Sommer E, Kozasa T, Srinivasula S, Alessi D, Offermanns S, Simon MI, Wu D. PRR5L degradation promotes mTORC2-mediated PKC-δ phosphorylation and cell migration downstream of Gα12. Nat Cell Biol. 2012 May 20;14(7):686-96. PMID:22609986 doi:10.1038/ncb2507
12. ↑ Jian SL, Hsieh HY, Liao CT, Yen TC, Nien SW, Cheng AJ, Juang JL. Gα₁₂ drives invasion of oral squamous cell carcinoma through up-regulation of proinflammatory cytokines. PLoS One. 2013 Jun 7;8(6):e66133. PMID:23762476 doi:10.1371/journal.pone.0066133
13. ↑ Yuan B, Cui J, Wang W, Deng K. Gα12/13 signaling promotes cervical cancer invasion through the RhoA/ROCK-JNK signaling axis. Biochem Biophys Res Commun. 2016 May 13;473(4):1240-1246. PMID:27084452 doi:10.1016/j.bbrc.2016.04.048