GNA12 explained

Guanine nucleotide-binding protein subunit alpha-12 is a protein that in humans is encoded by the GNA12 gene.^{[1] [2] [3]}

Interactions and functions

The GNA12 gene encodes the G₁₂ G protein alpha subunit. Together with GNA13, these two proteins comprise one of the four classes of heterotrimeric G protein alpha subunits.^[4] Heterotrimeric G proteins function in transducing hormone and neurotransmitter signals detected by cell surface G protein-coupled receptors to intracellular signaling pathways to modulate cell functions. G protein alpha subunits bind to guanine nucleotides and function in a regulatory cycle, and are active when bound to GTP but inactive and associated with the G beta-gamma complex when bound to GDP.^{[5] [6]}

Active GTP-bound G₁₂ alpha subunit interacts with and activates ARHGEF1,^[7] ARHGEF11,^{[8] [9]} and ARHGEF12.^{[10] [11]} These ARHGEF proteins function as guanine nucleotide exchange factors for the Rho small GTPases to regulate the actin cytoskeleton.^[12]

GNA12 also interacts with PPP5C,^[13] HSP90,^[14] Resistance to inhibitors of cholinesterase-8A (Ric-8A)^[15] and TEC.^[11]

See also

• G12/G13 alpha subunits
• G protein-coupled receptor
• Heterotrimeric G protein
• Rho family of GTPases

Notes and References

1. Chan AM, Fleming TP, McGovern ES, Chedid M, Miki T, Aaronson SA . Expression cDNA cloning of a transforming gene encoding the wild-type G alpha 12 gene product . Molecular and Cellular Biology . 13 . 2 . 762–8 . February 1993 . 8423800 . 358958 . 10.1128/mcb.13.2.762.
2. Kumar RN, Shore SK, Dhanasekaran N . Neoplastic transformation by the gep oncogene, Galpha12, involves signaling by STAT3 . Oncogene . 25 . 6 . 899–906 . February 2006 . 16247467 . 10.1038/sj.onc.1209132 . free .
3. Web site: Entrez Gene: GNA12 guanine nucleotide binding protein (G protein) alpha 12.
4. Strathmann MP, Simon MI . G alpha 12 and G alpha 13 subunits define a fourth class of G protein alpha subunits . Proc. Natl. Acad. Sci. U.S.A. . 88 . 13 . 5582–6 . 1991 . 1905812 . 10.1073/pnas.88.13.5582 . 51921 . 1991PNAS...88.5582S . free .
5. Gilman . AG . 1987 . G proteins: transducers of receptor-generated signals . Annual Review of Biochemistry . 56 . 615–649 . 10.1146/annurev.bi.56.070187.003151 . 3113327 .
6. Rodbell . M . 1995 . Nobel Lecture: Signal transduction: Evolution of an idea . Bioscience Reports . 15 . 3 . 117–133 . 10.1007/bf01207453 . 7579038 . 11025853 . 1519115 .
7. Johnson EN, Seasholtz TM, Waheed AA, Kreutz B, Suzuki N, Kozasa T, Jones TL, Brown JH, Druey KM . RGS16 inhibits signalling through the G alpha 13-Rho axis . Nature Cell Biology . 5 . 12 . 1095–103 . December 2003 . 14634662 . 10.1038/ncb1065 . 6798899 .
8. Fukuhara . S . Murga . C . Zohar . M . Igishi . T . Gutkind . JS . 1999-02-26 . A novel PDZ domain containing guanine nucleotide exchange factor links heterotrimeric G proteins to Rho . Journal of Biological Chemistry . 274 . 9 . 5868–5879 . 10.1074/jbc.274.9.5868 . 10026210 . free .
9. Rümenapp . U . Blomquist . A . Schwörer . G . Schablowski . H . Psoma . A . Jakobs . KH . 1999-10-15 . Rho-specific binding and guanine nucleotide exchange catalysis by KIAA0380, a dbl family member . FEBS Letters . 459 . 3 . 313–318 . 10.1016/s0014-5793(99)01270-3 . 10526156 . 8529412 .
10. Fukuhara S, Chikumi H, Gutkind JS . Leukemia-associated Rho guanine nucleotide exchange factor (LARG) links heterotrimeric G proteins of the G(12) family to Rho . FEBS Letters . 485 . 2–3 . 183–8 . November 2000 . 11094164 . 10.1016/S0014-5793(00)02224-9 . 7300556 . free .
11. Suzuki N, Nakamura S, Mano H, Kozasa T . Galpha 12 activates Rho GTPase through tyrosine-phosphorylated leukemia-associated RhoGEF . Proceedings of the National Academy of Sciences of the United States of America . 100 . 2 . 733–8 . January 2003 . 12515866 . 141065 . 10.1073/pnas.0234057100 . 2003PNAS..100..733S . free .
12. Dhanasekaran N, Dermott JM . Signaling by the G12 class of G proteins . Cell. Signal. . 8 . 4 . 235–45 . 1996 . 8842523 . 10.1016/0898-6568(96)00048-4 .
13. Yamaguchi Y, Katoh H, Mori K, Negishi M . Galpha(12) and Galpha(13) interact with Ser/Thr protein phosphatase type 5 and stimulate its phosphatase activity . Current Biology . 12 . 15 . 1353–8 . August 2002 . 12176367 . 10.1016/S0960-9822(02)01034-5 . 11485795 . free .
14. Vaiskunaite R, Kozasa T, Voyno-Yasenetskaya TA . Interaction between the G alpha subunit of heterotrimeric G(12) protein and Hsp90 is required for G alpha(12) signaling . The Journal of Biological Chemistry . 276 . 49 . 46088–93 . December 2001 . 11598136 . 10.1074/jbc.M108711200 . free .
15. Wang L, Guo D, Xing B, Zhang JJ, Shu HB, Guo L, Huang XY . Resistance to inhibitors of cholinesterase-8A (Ric-8A) is critical for growth factor receptor-induced actin cytoskeletal reorganization . The Journal of Biological Chemistry . 286 . 35 . 31055–61 . September 2011 . 21771786 . 10.1074/jbc.M111.253427 . 3162464. free .