Guanine nucleotide-binding protein subunit alpha-12

Definition:

Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. Activates effector molecule RhoA by binding and activating RhoGEFs (ARHGEF12/LARG). 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. Promotes tumor cell invasion and metastasis by activating RhoA/ROCK signaling pathway and up-regulating pro-inflammatory cytokine production. Inhibits CDH1-mediated cell adhesion in process independent from Rho activation. Together with NAPA promotes CDH5 localization to plasma membrane. May play a role in the control of cell migration through the TOR signaling cascade.

References:

[1]. Beate F Krakstad, et al. A role for Galpha12/Galpha13 in p120ctn regulation. Proc Natl Acad Sci U S A. 2004 Jul 13;101(28):10314-9. [Content Brief]

[2]. Thomas E Meigs, et al. Galpha12 and Galpha13 negatively regulate the adhesive functions of cadherin. J Biol Chem. 2002 Jul 5;277(27):24594-600. [Content Brief]

[3]. Patrick Kelly, et al. A role for the G12 family of heterotrimeric G proteins in prostate cancer invasion. J Biol Chem. 2006 Sep 8;281(36):26483-90. [Content Brief]

[4]. Nobuchika Suzuki, et al. 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. [Content Brief]

[5]. Patrick Kelly, et al. 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. [Content Brief]

[6]. Shiou-Ling Jian, et al. Gα₁₂ drives invasion of oral squamous cell carcinoma through up-regulation of proinflammatory cytokines. PLoS One. 2013 Jun 7;8(6):e66133. [Content Brief]

[7]. Xiaoqing Gan, et al. PRR5L degradation promotes mTORC2-mediated PKC-δ phosphorylation and cell migration downstream of Gα12. Nat Cell Biol. 2012 May 20;14(7):686-96. [Content Brief]

[8]. Bo Yuan, et al. 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. [Content Brief]

[9]. Katsunori Tateiwa, et al. Socius, a novel binding partner of Galpha12/13, promotes the Galpha12-induced RhoA activation. Biochem Biophys Res Commun. 2005 Nov 18;337(2):615-20. [Content Brief]

[10]. Vijay Yanamadala, et al. 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. [Content Brief]

[11]. Alexandra V Andreeva, et al. 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. [Content Brief]

[12]. Deguang Zhu, et al. 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. [Content Brief]

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