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Gene Review

Gna12  -  guanine nucleotide binding protein, alpha 12

Mus musculus

Synonyms: AI414047, AI504261, G alpha-12, G-protein subunit alpha-12, Galpha12, ...
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Disease relevance of Gna12

  • Our results indicate that it is cell type independent as the transient expression of Galpha12QL or the activation of Galpha12-coupled receptors stimulates the expression of PDGFRalpha in NIH 3T3 as well as in human astrocytoma 1321N1 cells [1].
  • Galpha12 and Galpha13 mediate differentiation of P19 mouse embryonal carcinoma cells in response to retinoic acid [2].
  • Finally, we demonstrate that the expression of Galpha12 is significantly up-regulated in the earliest stages of breast cancer, implying that amplification of G12 signaling may be an early event in breast cancer progression [3].
  • Initial experiments were designed to examine the role of pertussis toxin-sensitive G proteins, namely Galphai/o, as well as pertussis toxin-insensitive G proteins, namely Galpha12/13, in 5-HT-induced AA release [4].

High impact information on Gna12

  • Here we demonstrate that Galphas and Galphai, but neither Galphaq, Galpha12 nor Gbetay, directly stimulate the kinase activity of downregulated c-Src [5].
  • In mouse embryonic fibroblasts, the pSLIK platform was used to conditionally deplete the expression of the heterotrimeric G proteins Galpha12 and Galpha13 both singly and in combination, demonstrating the Galpha13 dependence of serum response element-mediated transcription [6].
  • The DH-domain-deletion mutant also suppressed thrombin- and lysophosphatidic acid-induced SRF activation in NIH 3T3 cells, probably by inhibition of Galpha12/13 [7].
  • Transactivation of platelet-derived growth factor receptor alpha by the GTPase-deficient activated mutant of Galpha12 [1].
  • Using microarray analysis, we have previously identified a role for platelet-derived growth factor receptor alpha (PDGFRalpha) in Galpha12-mediated cell growth (R. N. Kumar et al., Cell Biochem. Biophys. 41:63-73, 2004) [1].

Biological context of Gna12


Anatomical context of Gna12


Associations of Gna12 with chemical compounds

  • Therefore, the thrombin, LPA, thromboxane A2, and endothelin receptors may be able to couple to Galpha12/13 [15].
  • G alpha 12/13- and reactive oxygen species-dependent activation of c-Jun NH2-terminal kinase and p38 mitogen-activated protein kinase by angiotensin receptor stimulation in rat neonatal cardiomyocytes [16].
  • Pretreatment of Galpha12WT-NIH3T3 cells with suramin (100 microM), a receptor-uncoupling agent, inhibited LPA-stimulated proliferation of these cells by 55% demonstrating the signal coupling between cell surface LPAR and Galpha12 in the neoplastic proliferation of NIH3T3 cells [9].
  • In the present study, using guanine nucleotide exchange assay and GST-TPR binding assay, we show that the treatment of Galpha12WT-NIH3T3 with 2 muM LPA leads to the activation of Galpha12 [9].
  • However, tyrphostin A25 failed to inhibit the Galpha12-induced neuronal morphological changes [17].

Regulatory relationships of Gna12


Other interactions of Gna12


Analytical, diagnostic and therapeutic context of Gna12


  1. Transactivation of platelet-derived growth factor receptor alpha by the GTPase-deficient activated mutant of Galpha12. Kumar, R.N., Ha, J.H., Radhakrishnan, R., Dhanasekaran, D.N. Mol. Cell. Biol. (2006) [Pubmed]
  2. Galpha12 and Galpha13 mediate differentiation of P19 mouse embryonal carcinoma cells in response to retinoic acid. Jho, E.H., Malbon, C.C. J. Biol. Chem. (1997) [Pubmed]
  3. The G12 family of heterotrimeric G proteins promotes breast cancer invasion and metastasis. Kelly, P., Moeller, B.J., Juneja, J., Booden, M.A., Der, C.J., Daaka, Y., Dewhirst, M.W., Fields, T.A., Casey, P.J. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  4. A complex signaling cascade links the serotonin2A receptor to phospholipase A2 activation: the involvement of MAP kinases. Kurrasch-Orbaugh, D.M., Parrish, J.C., Watts, V.J., Nichols, D.E. J. Neurochem. (2003) [Pubmed]
  5. Src tyrosine kinase is a novel direct effector of G proteins. Ma, Y.C., Huang, J., Ali, S., Lowry, W., Huang, X.Y. Cell (2000) [Pubmed]
  6. A single lentiviral vector platform for microRNA-based conditional RNA interference and coordinated transgene expression. Shin, K.J., Wall, E.A., Zavzavadjian, J.R., Santat, L.A., Liu, J., Hwang, J.I., Rebres, R., Roach, T., Seaman, W., Simon, M.I., Fraser, I.D. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  7. Guanine nucleotide exchange factor GEF115 specifically mediates activation of Rho and serum response factor by the G protein alpha subunit Galpha13. Mao, J., Yuan, H., Xie, W., Wu, D. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  8. Thrombin induces nitric-oxide synthase via Galpha12/13-coupled protein kinase C-dependent I-kappaBalpha phosphorylation and JNK-mediated I-kappaBalpha degradation. Kang, K.W., Choi, S.Y., Cho, M.K., Lee, C.H., Kim, S.G. J. Biol. Chem. (2003) [Pubmed]
  9. Mitogenic signaling by lysophosphatidic acid (LPA) involves Galpha12. Radhika, V., Hee Ha, J., Jayaraman, M., Tsim, S.T., Dhanasekaran, N. Oncogene (2005) [Pubmed]
  10. Differential involvement of Galpha12 and Galpha13 in receptor-mediated stress fiber formation. Gohla, A., Offermanns, S., Wilkie, T.M., Schultz, G. J. Biol. Chem. (1999) [Pubmed]
  11. G protein gene expression during mouse oocyte growth and maturation, and preimplantation embryo development. Williams, C.J., Schultz, R.M., Kopf, G.S. Mol. Reprod. Dev. (1996) [Pubmed]
  12. The small GTP-binding protein Rho links G protein-coupled receptors and Galpha12 to the serum response element and to cellular transformation. Fromm, C., Coso, O.A., Montaner, S., Xu, N., Gutkind, J.S. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  13. Activation of RhoA by lysophosphatidic acid and Galpha12/13 subunits in neuronal cells: induction of neurite retraction. Kranenburg, O., Poland, M., van Horck, F.P., Drechsel, D., Hall, A., Moolenaar, W.H. Mol. Biol. Cell (1999) [Pubmed]
  14. Galpha12/13 is essential for directed cell migration and localized Rho-Dia1 function. Goulimari, P., Kitzing, T.M., Knieling, H., Brandt, D.T., Offermanns, S., Grosse, R. J. Biol. Chem. (2005) [Pubmed]
  15. Specific involvement of G proteins in regulation of serum response factor-mediated gene transcription by different receptors. Mao, J., Yuan, H., Xie, W., Simon, M.I., Wu, D. J. Biol. Chem. (1998) [Pubmed]
  16. G alpha 12/13- and reactive oxygen species-dependent activation of c-Jun NH2-terminal kinase and p38 mitogen-activated protein kinase by angiotensin receptor stimulation in rat neonatal cardiomyocytes. Nishida, M., Tanabe, S., Maruyama, Y., Mangmool, S., Urayama, K., Nagamatsu, Y., Takagahara, S., Turner, J.H., Kozasa, T., Kobayashi, H., Sato, Y., Kawanishi, T., Inoue, R., Nagao, T., Kurose, H. J. Biol. Chem. (2005) [Pubmed]
  17. Constitutively active Galpha12, Galpha13, and Galphaq induce Rho-dependent neurite retraction through different signaling pathways. Katoh, H., Aoki, J., Yamaguchi, Y., Kitano, Y., Ichikawa, A., Negishi, M. J. Biol. Chem. (1998) [Pubmed]
  18. Glycogen synthase kinase-3 is activated in neuronal cells by Galpha12 and Galpha13 by Rho-independent and Rho-dependent mechanisms. Sayas, C.L., Avila, J., Wandosell, F. J. Neurosci. (2002) [Pubmed]
  19. Differential regulation of Jun N-terminal kinase and p38MAP kinase by Galpha12. Dermott, J.M., Ha, J.H., Lee, C.H., Dhanasekaran, N. Oncogene (2004) [Pubmed]
  20. CCK-A receptor activates RhoA through G alpha 12/13 in NIH3T3 cells. Le Page, S.L., Bi, Y., Williams, J.A. Am. J. Physiol., Cell Physiol. (2003) [Pubmed]
  21. Dependence of activated Galpha12-induced G1 to S phase cell cycle progression on both Ras/mitogen-activated protein kinase and Ras/Rac1/Jun N-terminal kinase cascades in NIH3T3 fibroblasts. Mitsui, H., Takuwa, N., Kurokawa, K., Exton, J.H., Takuwa, Y. J. Biol. Chem. (1997) [Pubmed]
  22. Galpha12 stimulates c-Jun NH2-terminal kinase through the small G proteins Ras and Rac. Collins, L.R., Minden, A., Karin, M., Brown, J.H. J. Biol. Chem. (1996) [Pubmed]
  23. The G-protein G13 but not G12 mediates signaling from lysophosphatidic acid receptor via epidermal growth factor receptor to Rho. Gohla, A., Harhammer, R., Schultz, G. J. Biol. Chem. (1998) [Pubmed]
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