title: Receptor-independent activators of heterotrimeric G-proteins.
abstract: Heterotrimeric G-protein signalling systems are primarily activated via cell surface receptors possessing the seven membrane span motif. Several observations suggest the existence of other modes of input to such signalling systems either downstream of effectors or at the level of G-proteins themselves. Using a functional screen based upon the pheromone response pathway in Saccharomyces cerevisiae, we identified three proteins, AGS1-3 (for Activators of G-protein Signalling), that activated heterotrimeric G-protein signalling pathways in the absence of a typical receptor. AGS1 defines a distinct member of the super family of ras related proteins. AGS2 is identical to mouse Tctex1, a protein that exists as a light chain component of the cytoplasmic motor protein dynein and subserves as yet undefined functions in cell signalling pathways. AGS3 possesses a series of tetratrico repeat motifs and a series of four amino acid repeats termed G-protein regulatory motifs. The GPR motifs are found in a number of proteins that interact with and regulate Galpha. Although each AGS protein activates G-protein signaling, they do so by different mechanisms within the context of the G-protein activation/deactivation cycle. AGS proteins provide unexpected mechanisms for input to heterotrimeric G-protein signalling pathways.
authors.affiliation: Department of Pharmacology, Medical University of South Carolina, Charleston 29425, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Cismowski
authors.forename: A
authors.initials: A
authors.lastname: Takesono
authors.forename: M L
authors.initials: ML
authors.lastname: Bernard
authors.forename: E
authors.initials: E
authors.lastname: Duzic
authors.forename: S M
authors.initials: SM
authors.lastname: Lanier
mesh_terms: D000818:Animals; D002628:Chemoreceptor Cells / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D020962:Heterotrimeric GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C400132:RASD1 protein, human; D011956:Receptors, Cell Surface; D019204:GTP-Binding Proteins; C498511:Rasd1 protein, mouse; D020962:Heterotrimeric GTP-Binding Proteins; D018631:ras Proteins