title: Activation of heterotrimeric G-protein signaling by a ras-related protein. Implications for signal integration.
abstract: Utilizing a functional screen in the yeast Saccharomyces cerevisiae we identified mammalian proteins that activate heterotrimeric G-protein signaling pathways in a receptor-independent fashion. One of the identified activators, termed AGS1 (for activator of G-protein signaling), is a human Ras-related G-protein that defines a distinct subgroup of the Ras superfamily. Expression of AGS1 in yeast and in mammalian cells results in specific activation of Galpha(i)/Galpha(o) heterotrimeric signaling pathways. In addition, the in vivo and in vitro properties of AGS1 are consistent with it functioning as a direct guanine nucleotide exchange factor for Galpha(i)/Galpha(o). AGS1 thus presents a unique mechanism for signal integration via heterotrimeric G-protein signaling pathways.
authors.affiliation: OSI Pharmaceuticals, Tarrytown, New York 10591, the Department of Pharmacology, Medical University of South Carolina, Charleston, South Carolina 29425, USA. mcismowski@neurocrine.com
authors.forename: M J
authors.initials: MJ
authors.lastname: Cismowski
authors.forename: C
authors.initials: C
authors.lastname: Ma
authors.forename: C
authors.initials: C
authors.lastname: Ribas
authors.forename: X
authors.initials: X
authors.lastname: Xie
authors.forename: M
authors.initials: M
authors.lastname: Spruyt
authors.forename: J S
authors.initials: JS
authors.lastname: Lizano
authors.forename: S M
authors.initials: SM
authors.lastname: Lanier
authors.forename: E
authors.initials: E
authors.lastname: Duzic
mesh_terms: D000595:Amino Acid Sequence; D018076:DNA, Complementary; D051960:GTP-Binding Protein alpha Subunit, Gi2; D044385:GTP-Binding Protein alpha Subunits; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000378:metabolism; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006868:Hydrolysis; D008969:Molecular Sequence Data; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D018076:DNA, Complementary; D044385:GTP-Binding Protein alpha Subunits; D020662:Guanine Nucleotide Exchange Factors; D011518:Proto-Oncogene Proteins; C400132:RASD1 protein, human; C084618:olfactory G protein subunit alpha olf; D006160:Guanosine Triphosphate; D019204:GTP-Binding Proteins; C498015:GNAI2 protein, human; D051960:GTP-Binding Protein alpha Subunit, Gi2; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D020962:Heterotrimeric GTP-Binding Proteins; D018631:ras Proteins