This gene encodes a member of the regulator of G-protein signaling family. This protein contains a conserved, 120 amino acid motif called the RGS domain and a cysteine-rich region. The protein attenuates the signaling activity of G-proteins by binding to activated, GTP-bound G alpha subunits and acting as a GTPase activating protein (GAP), increasing the rate of conversion of the GTP to GDP. This hydrolysis allows the G alpha subunits to bind G beta/gamma subunit heterodimers, forming inactive G-protein heterotrimers, thereby terminating the signal.[2] Along with RGS4, RGS9 and RGS14,[3][4] RGS17 plays an important role in termination of signalling by mu opioid receptors and development of tolerance to opioid analgesic drugs.[5][6]
Clinical significance
RGS17 is a putative lung cancer susceptibility gene in the lung cancer associated locus on chromosome 6q in humans.[7] RGS17 is overexpressed in lung and prostate cancers, induces cAMP production, CREB phosphorylation and CREB responsive gene expression[2]. Expression of RGS17 is required for maintenance of proliferation in lung tumor cell lines.[8]
References
↑Jordan JD, Carey KD, Stork PJ, Iyengar R (Jul 1999). "Modulation of rap activity by direct interaction of Galpha(o) with Rap1 GTPase-activating protein". The Journal of Biological Chemistry. 274 (31): 21507–10. doi:10.1074/jbc.274.31.21507. PMID10419452.
↑Garzón J, Rodríguez-Muñoz M, de la Torre-Madrid E, Sánchez-Blázquez P (Jun 2005). "Effector antagonism by the regulators of G protein signalling (RGS) proteins causes desensitization of mu-opioid receptors in the CNS". Psychopharmacology. 180 (1): 1–11. doi:10.1007/s00213-005-2248-9. PMID15830230.
↑Rodríguez-Muñoz M, de la Torre-Madrid E, Gaitán G, Sánchez-Blázquez P, Garzón J (Dec 2007). "RGS14 prevents morphine from internalizing Mu-opioid receptors in periaqueductal gray neurons". Cellular Signalling. 19 (12): 2558–71. doi:10.1016/j.cellsig.2007.08.003. PMID17825524.
↑Garzón J, Rodríguez-Muñoz M, López-Fando A, Sánchez-Blázquez P (Sep 2005). "The RGSZ2 protein exists in a complex with mu-opioid receptors and regulates the desensitizing capacity of Gz proteins". Neuropsychopharmacology. 30 (9): 1632–48. doi:10.1038/sj.npp.1300726. PMID15827571.
Mao H, Zhao Q, Daigle M, Ghahremani MH, Chidiac P, Albert PR (Jun 2004). "RGS17/RGSZ2, a novel regulator of Gi/o, Gz, and Gq signaling". The Journal of Biological Chemistry. 279 (25): 26314–22. doi:10.1074/jbc.M401800200. PMID15096504.
Larminie C, Murdock P, Walhin JP, Duckworth M, Blumer KJ, Scheideler MA, Garnier M (Mar 2004). "Selective expression of regulators of G-protein signaling (RGS) in the human central nervous system". Brain Research. Molecular Brain Research. 122 (1): 24–34. doi:10.1016/j.molbrainres.2003.11.014. PMID14992813.
Sierra DA, Gilbert DJ, Householder D, Grishin NV, Yu K, Ukidwe P, Barker SA, He W, Wensel TG, Otero G, Brown G, Copeland NG, Jenkins NA, Wilkie TM (Feb 2002). "Evolution of the regulators of G-protein signaling multigene family in mouse and human". Genomics. 79 (2): 177–85. doi:10.1006/geno.2002.6693. PMID11829488.
