Activation of heterotrimeric G-protein signaling by a ras-related protein. Implications for signal integration.
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.
Cismowski
M J
MJ
OSI Pharmaceuticals, Tarrytown, New York 10591, the Department of Pharmacology, Medical University of South Carolina, Charleston, South Carolina 29425, USA. mcismowski@neurocrine.com
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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*
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