GPR1 encodes a putative G protein-coupled receptor that associates with the Gpa2p Galpha subunit and functions in a Ras-independent pathway.
The yeast RAS1 and RAS2 genes appear to be involved in control of cell growth in response to nutrients. Here we show that this growth control also involves a signal mediated by the heterotrimeric G protein alpha subunit homolog encoded by GPA2. A GPA2 null allele conferred a severe growth defect on cells containing a null allele of RAS2, although either mutation alone had little effect on growth rate. A constitutive allele of GPA2 could stimulate growth of a strain lacking both RAS genes. Constitutive GPA2 conferred heat shock sensitivity on both wild-type cells and cells lacking RAS function, but had no effect in a strain containing a null allele of SCH9, which encodes a kinase related to protein kinase A. The GPR1 gene was isolated and was found to encode a protein with the characteristics of a G protein-coupled receptor. Double Deltagpr1 Deltaras2 mutants displayed a severe growth defect that was suppressed by expression of the constitutive allele of GPA2, confirming that GPR1 acts upstream of GPA2. Gpr1p is expressed on the cell surface and requires sequences in the membrane-proximal region of its third cytoplasmic loop for function, as expected for a G protein-coupled receptor. GPR1 RNA was induced when cells were starved for nitrogen and amino acids. These results are consistent with a model in which the GPR1/GPA2 pathway activates the Sch9p kinase to generate a response that acts in parallel with that generated by the Ras/cAMP pathway, resulting in the integration of nutrient signals.
Xue
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Department of Cell Biology and Anatomy, Mount Sinai School of Medicine, New York, NY 10029, USA.
Batlle
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Hirsch
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JP
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000502:physiology; D002462:Cell Membrane / Q000737:chemistry; D000242:Cyclic AMP / Q000502:physiology; D003593:Cytoplasm / Q000737:chemistry; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D044385:GTP-Binding Protein alpha Subunits; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal / Q000502:physiology; D011905:Genes, ras / Q000502:physiology*; D018869:Heat-Shock Response; D020962:Heterotrimeric GTP-Binding Proteins; D008969:Molecular Sequence Data; D009154:Mutation; D009584:Nitrogen; D010641:Phenotype; D011494:Protein Kinases / Q000235:genetics / Q000502:physiology; D012331:RNA, Fungal / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D011956:Receptors, Cell Surface / Q000032:analysis / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled; D011993:Recombinant Fusion Proteins; D012441:Saccharomyces cerevisiae / Q000378:metabolism / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D013172:Spores, Fungal; D018631:ras Proteins / Q000502:physiology
D000596:Amino Acids; D005656:Fungal Proteins; C109334:GPR1 protein, S cerevisiae; D044385:GTP-Binding Protein alpha Subunits; D012331:RNA, Fungal; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D000242:Cyclic AMP; D011494:Protein Kinases; C071569:SCH9 protein kinase; D019204:GTP-Binding Proteins; C083907:Gpa2 protein, S cerevisiae; D020962:Heterotrimeric GTP-Binding Proteins; C489014:RAS1 protein, S cerevisiae; C489015:RAS2 protein, S cerevisiae; D018631:ras Proteins; D009584:Nitrogen