Complexes of the G protein subunit gbeta 5 with the regulators of G protein signaling RGS7 and RGS9. Characterization in native tissues and in transfected cells - PubMed (original) (raw)
. 2000 Aug 11;275(32):24872-80.
doi: 10.1074/jbc.M001535200.
Affiliations
- PMID: 10840031
- DOI: 10.1074/jbc.M001535200
Free article
Complexes of the G protein subunit gbeta 5 with the regulators of G protein signaling RGS7 and RGS9. Characterization in native tissues and in transfected cells
D S Witherow et al. J Biol Chem. 2000.
Free article
Abstract
A novel protein class, termed regulators of G protein signaling (RGS), negatively regulates G protein pathways through a direct interaction with Galpha subunits and stimulation of GTP hydrolysis. An RGS subfamily including RGS6, -7, -9, and -11, which contain a characteristic Ggamma -like domain, also has the unique ability to interact with the G protein beta subunit Gbeta(5). Here, we examined the behavior of Gbeta(5), RGS7, RGS9, and Galpha in tissue extracts using immunoprecipitation and conventional chromatography. Native Gbeta(5) and RGS7 from brain, as well as photoreceptor-specific Gbeta(5)L and RGS9, always co-purified as tightly associated dimers, and neither RGS-free Gbeta(5) nor Gbeta(5)-free RGS could be detected. Co-expression in COS-7 cells of Gbeta(5) dramatically increased the protein level of RGS7 and vice versa, indicating that cells maintain Gbeta(5):RGS stoichiometry in a manner similar to Gbetagamma complexes. This mechanism is non-transcriptional and is based on increased protein stability upon dimerization. Thus, analysis of native Gbeta(5)-RGS and their coupled expression argue that in vivo, Gbeta(5) and Ggamma-like domain-containing RGSs only exist as heterodimers. Native Gbeta(5)-RGS7 did not co-precipitate or co-purify with Galpha(o) or Galpha(q); nor did Gbeta(5)L-RGS9 with Galpha(t). However, in transfected cells, RGS7 and Gbeta(5)-RGS7 inhibited Galpha(q)-mediated Ca(2+) response to muscarinic M3 receptor activation. Thus, Gbeta(5)-RGS dimers differ from other RGS proteins in that they do not bind to Galpha with high affinity, but they can still inhibit G protein signaling.
Similar articles
- RGS6, RGS7, RGS9, and RGS11 stimulate GTPase activity of Gi family G-proteins with differential selectivity and maximal activity.
Hooks SB, Waldo GL, Corbitt J, Bodor ET, Krumins AM, Harden TK. Hooks SB, et al. J Biol Chem. 2003 Mar 21;278(12):10087-93. doi: 10.1074/jbc.M211382200. Epub 2003 Jan 16. J Biol Chem. 2003. PMID: 12531899 - Two RGS proteins that inhibit Galpha(o) and Galpha(q) signaling in C. elegans neurons require a Gbeta(5)-like subunit for function.
Chase DL, Patikoglou GA, Koelle MR. Chase DL, et al. Curr Biol. 2001 Feb 20;11(4):222-31. doi: 10.1016/s0960-9822(01)00071-9. Curr Biol. 2001. PMID: 11250150 - Ggamma subunit-selective G protein beta 5 mutant defines regulators of G protein signaling protein binding requirement for nuclear localization.
Rojkova AM, Woodard GE, Huang TC, Combs CA, Zhang JH, Simonds WF. Rojkova AM, et al. J Biol Chem. 2003 Apr 4;278(14):12507-12. doi: 10.1074/jbc.M207302200. Epub 2003 Jan 24. J Biol Chem. 2003. PMID: 12551930 - The GAPs, GEFs, and GDIs of heterotrimeric G-protein alpha subunits.
Siderovski DP, Willard FS. Siderovski DP, et al. Int J Biol Sci. 2005;1(2):51-66. doi: 10.7150/ijbs.1.51. Epub 2005 Apr 1. Int J Biol Sci. 2005. PMID: 15951850 Free PMC article. Review. - Fluorescence-based assays for RGS box function.
Willard FS, Kimple RJ, Kimple AJ, Johnston CA, Siderovski DP. Willard FS, et al. Methods Enzymol. 2004;389:56-71. doi: 10.1016/S0076-6879(04)89004-9. Methods Enzymol. 2004. PMID: 15313559 Review.
Cited by
- The association of GNB5 with Alzheimer disease revealed by genomic analysis restricted to variants impacting gene function.
Zhang J, Pandey M, Awe A, Lue N, Kittock C, Fikse E, Degner K, Staples J, Mokhasi N, Chen W, Yang Y, Adikaram P, Jacob N, Greenfest-Allen E, Thomas R, Bomeny L, Zhang Y, Petros TJ, Wang X, Li Y, Simonds WF. Zhang J, et al. Am J Hum Genet. 2024 Mar 7;111(3):473-486. doi: 10.1016/j.ajhg.2024.01.005. Epub 2024 Feb 13. Am J Hum Genet. 2024. PMID: 38354736 Free PMC article. - Molecular Influence of Resiniferatoxin on the Urinary Bladder Wall Based on Differential Gene Expression Profiling.
Lepiarczyk E, Paukszto Ł, Wiszpolska M, Łopieńska-Biernat E, Bossowska A, Majewski MK, Majewska M. Lepiarczyk E, et al. Cells. 2023 Jan 31;12(3):462. doi: 10.3390/cells12030462. Cells. 2023. PMID: 36766804 Free PMC article. - Arginylation Regulates G-protein Signaling in the Retina.
Fina ME, Wang J, Vedula P, Tang HY, Kashina A, Dong DW. Fina ME, et al. Front Cell Dev Biol. 2022 Jan 21;9:807345. doi: 10.3389/fcell.2021.807345. eCollection 2021. Front Cell Dev Biol. 2022. PMID: 35127722 Free PMC article. - Arginyltransferase (Ate1) regulates the RGS7 protein level and the sensitivity of light-evoked ON-bipolar responses.
Fina ME, Wang J, Nikonov SS, Sterling S, Vardi N, Kashina A, Dong DW. Fina ME, et al. Sci Rep. 2021 Apr 30;11(1):9376. doi: 10.1038/s41598-021-88628-3. Sci Rep. 2021. PMID: 33931669 Free PMC article. - Subtype-dependent regulation of Gβγ signalling.
Tennakoon M, Senarath K, Kankanamge D, Ratnayake K, Wijayaratna D, Olupothage K, Ubeysinghe S, Martins-Cannavino K, Hébert TE, Karunarathne A. Tennakoon M, et al. Cell Signal. 2021 Jun;82:109947. doi: 10.1016/j.cellsig.2021.109947. Epub 2021 Feb 11. Cell Signal. 2021. PMID: 33582184 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Miscellaneous