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G-protein signaling: back to the future

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Abstract.

Heterotrimeric G-proteins are intracellular partners of G-protein-coupled receptors (GPCRs). GPCRs act on inactive Gα·GDP/Gβγ heterotrimers to promote GDP release and GTP binding, resulting in liberation of Gα from Gβγ. Gα·GTP and Gβγ target effectors including adenylyl cyclases, phospholipases and ion channels. Signaling is terminated by intrinsic GTPase activity of Gα and heterotrimer reformation — a cycle accelerated by ‘regulators of G-protein signaling’ (RGS proteins). Recent studies have identified several unconventional G-protein signaling pathways that diverge from this standard model. Whereas phospholipase C (PLC) β is activated by Gαq and Gβγ, novel PLC isoforms are regulated by both heterotrimeric and Ras-superfamily G-proteins. An Arabidopsis protein has been discovered containing both GPCR and RGS domains within the same protein. Most surprisingly, a receptor-independent Gα nucleotide cycle that regulates cell division has been delineated in both Caenorhabditis elegans and Drosophila melanogaster. Here, we revisit classical heterotrimeric G-protein signaling and explore these new, non-canonical G-protein signaling pathways.

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Acknowledgement

We thank Christopher A. Johnston for critical appraisal of this review. C.R.M. and F.S.W. are postdoctoral fellows of the Natural Sciences and Engineering Council of Canada and the American Heart Association, respectively. R.J.K. acknowledges predoctoral fellowship support from the NIMH F30 MH64319. Work in the Siderovski laboratory is funded by U.S. National Institutes of Health grants GM062338 and GM065533.

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  1. Department of Pharmacology, Lineberger Comprehensive Cancer Center, and UNC Neuroscience Center, The University of North Carolina at Chapel Hill, 1106 Mary Ellen Jones Building, Chapel Hill, North Carolina, 27599-7365, USA

    C. R. McCudden, M. D. Hains, R. J. Kimple, D. P. Siderovski & F. S. Willard

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  1. C. R. McCudden
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  2. M. D. Hains
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Correspondence to D. P. Siderovski.

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Received 21 October 2004; received after revision 20 November 2004; accepted 30 November 2004

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McCudden, C.R., Hains, M.D., Kimple, R.J. et al. G-protein signaling: back to the future. CMLS, Cell. Mol. Life Sci. 62, 551–577 (2005). https://doi.org/10.1007/s00018-004-4462-3

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  • DOI: https://doi.org/10.1007/s00018-004-4462-3

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