Signalling Mechanisms of RhoGTPase Regulation by the Heterotrimeric G Proteins G12 and G13

Overview

Journal J Biochem

Publisher Oxford University Press

Specialty Biochemistry

Date 2011 Aug 30

PMID 21873336

Citations 42

Authors

Tohru Kozasa

Nicole Hajicek

Christina R Chow

Nobuchika Suzuki

Affiliations

Soon will be listed here.

Abstract

G protein-mediated signal transduction can transduce signals from a large variety of extracellular stimuli into cells and is the most widely used mechanism for cell communication at the membrane. The RhoGTPase family has been well established as key regulators of cell growth, differentiation and cell shape changes. Among G protein-mediated signal transduction, G12/13-mediated signalling is one mechanism to regulate RhoGTPase activity in response to extracellular stimuli. The alpha subunits of G12 or G13 have been shown to interact with members of the RH domain containing guanine nucleotide exchange factors for Rho (RH-RhoGEF) family of proteins to directly connect G protein-mediated signalling and RhoGTPase signalling. The G12/13-RH-RhoGEF signalling mechanism is well conserved over species and is involved in critical steps for cell physiology and disease conditions, including embryonic development, oncogenesis and cancer metastasis. In this review, we will summarize current progress on this important signalling mechanism.

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References

Taya S, Inagaki N, Sengiku H, Makino H, Iwamatsu A, Urakawa I . Direct interaction of insulin-like growth factor-1 receptor with leukemia-associated RhoGEF. J Cell Biol. 2001; 155(5):809-20. PMC: 2150867. DOI: 10.1083/jcb.200106139. View

Bhattacharyya R, Wedegaertner P . Characterization of G alpha 13-dependent plasma membrane recruitment of p115RhoGEF. Biochem J. 2003; 371(Pt 3):709-20. PMC: 1223324. DOI: 10.1042/BJ20021897. View

Singer W, Miller R, Sternweis P . Purification and characterization of the alpha subunit of G13. J Biol Chem. 1994; 269(31):19796-802. View

Girkontaite I, Missy K, Sakk V, Harenberg A, Tedford K, Potzel T . Lsc is required for marginal zone B cells, regulation of lymphocyte motility and immune responses. Nat Immunol. 2001; 2(9):855-62. DOI: 10.1038/ni0901-855. View

Derewenda U, Oleksy A, Stevenson A, Korczynska J, Dauter Z, Somlyo A . The crystal structure of RhoA in complex with the DH/PH fragment of PDZRhoGEF, an activator of the Ca(2+) sensitization pathway in smooth muscle. Structure. 2004; 12(11):1955-65. DOI: 10.1016/j.str.2004.09.003. View

Jiang Y, Ma W, Wan Y, Kozasa T, Hattori S, Huang X . The G protein G alpha12 stimulates Bruton's tyrosine kinase and a rasGAP through a conserved PH/BM domain. Nature. 1998; 395(6704):808-13. DOI: 10.1038/27454. View

Kozasa T, Jiang X, Hart M, Sternweis P, Singer W, GILMAN A . p115 RhoGEF, a GTPase activating protein for Galpha12 and Galpha13. Science. 1998; 280(5372):2109-11. DOI: 10.1126/science.280.5372.2109. View

Whitehead I, Khosravi-Far R, Kirk H, Der C, Kay R . Expression cloning of lsc, a novel oncogene with structural similarities to the Dbl family of guanine nucleotide exchange factors. J Biol Chem. 1996; 271(31):18643-50. DOI: 10.1074/jbc.271.31.18643. View

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; 100(2):733-8. PMC: 141065. DOI: 10.1073/pnas.0234057100. View

10.

Aittaleb M, Boguth C, Tesmer J . Structure and function of heterotrimeric G protein-regulated Rho guanine nucleotide exchange factors. Mol Pharmacol. 2009; 77(2):111-25. PMC: 2812070. DOI: 10.1124/mol.109.061234. View

11.

Chen Z, Singer W, Danesh S, Sternweis P, Sprang S . Recognition of the activated states of Galpha13 by the rgRGS domain of PDZRhoGEF. Structure. 2008; 16(10):1532-43. PMC: 2586972. DOI: 10.1016/j.str.2008.07.009. View

12.

Gohla A, Schultz G, Offermanns S . Role for G(12)/G(13) in agonist-induced vascular smooth muscle cell contraction. Circ Res. 2000; 87(3):221-7. DOI: 10.1161/01.res.87.3.221. View

13.

Fukuhara S, Chikumi H, Gutkind J . Leukemia-associated Rho guanine nucleotide exchange factor (LARG) links heterotrimeric G proteins of the G(12) family to Rho. FEBS Lett. 2000; 485(2-3):183-8. DOI: 10.1016/s0014-5793(00)02224-9. View

14.

Ponimaskin E, Behn H, Adarichev V, Voyno-Yasenetskaya T, Offermanns S, Schmidt M . Acylation of Galpha(13) is important for its interaction with thrombin receptor, transforming activity and actin stress fiber formation. FEBS Lett. 2000; 478(1-2):173-7. DOI: 10.1016/s0014-5793(00)01845-7. View

15.

Hart M, Sharma S, Elmasry N, Qiu R, McCabe P, Polakis P . Identification of a novel guanine nucleotide exchange factor for the Rho GTPase. J Biol Chem. 1996; 271(41):25452-8. DOI: 10.1074/jbc.271.41.25452. View

16.

Chen Z, Singer W, Wells C, Sprang S, Sternweis P . Mapping the Galpha13 binding interface of the rgRGS domain of p115RhoGEF. J Biol Chem. 2003; 278(11):9912-9. DOI: 10.1074/jbc.M212695200. View

17.

Boettner B, Van Aelst L . The role of Rho GTPases in disease development. Gene. 2002; 286(2):155-74. DOI: 10.1016/s0378-1119(02)00426-2. View

18.

Lappano R, Maggiolini M . G protein-coupled receptors: novel targets for drug discovery in cancer. Nat Rev Drug Discov. 2011; 10(1):47-60. DOI: 10.1038/nrd3320. View

19.

Zizer E, Beilke S, Bauerle T, Schilling K, Mohnle U, Adler G . Loss of Lsc/p115 protein leads to neuronal hypoplasia in the esophagus and an achalasia-like phenotype in mice. Gastroenterology. 2010; 139(4):1344-54. DOI: 10.1053/j.gastro.2010.06.041. View

20.

Yau D, Yokoyama N, Goshima Y, Siddiqui Z, Siddiqui S, Kozasa T . Identification and molecular characterization of the G alpha12-Rho guanine nucleotide exchange factor pathway in Caenorhabditis elegans. Proc Natl Acad Sci U S A. 2003; 100(25):14748-53. PMC: 299794. DOI: 10.1073/pnas.2533143100. View