G-protein signaling: Back to the future

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

Research output: Contribution to journalReview articlepeer-review

354 Scopus citations


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.

Original languageEnglish
Pages (from-to)551-577
Number of pages27
JournalCellular and Molecular Life Sciences
Issue number5
StatePublished - Mar 2005


  • Asymmetric cell division
  • G-protein
  • GoLoco motif
  • Phospholipase C
  • RGS proteins


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