Edg-2/Vzg-1 Couples to the Yeast Pheromone Response Pathway Selectively in Response to Lysophosphatidic Acid
1998; Elsevier BV; Volume: 273; Issue: 3 Linguagem: Inglês
10.1074/jbc.273.3.1506
ISSN1083-351X
AutoresJames R. Erickson, Jason Wu, John Goddard, Gábor Tigyi, Katsumasa Kawanishi, Licia Tomei, Michael Kiefer,
Tópico(s)Lipid Membrane Structure and Behavior
ResumoWe have functionally expressed the human cDNA encoding the putative lysophosphatidic acid (LPA) receptor Edg-2 (Vzg-1) in Saccharomyces cerevisiae in an attempt to determine the agonist specificity of this G-protein-coupled receptor. LPA activated the pheromone response pathway in S. cerevisiae expressing Edg-2 in a time- and dose-dependent manner as determined by induction of a pheromone-responsive FUS1::lacZ reporter gene. LPA-mediated activation of the pheromone response pathway was dependent on mutational inactivation of the SST2 gene, the GTPase-activating protein for the yeast G α protein (the GPA1 gene product). This indicates that, in sst2Δ yeast cells, Edg-2 can efficiently couple to the yeast heterotrimeric G-protein in response to LPA and activate the yeast mitogen-activated protein kinase pathway. The Edg-2 receptor showed a high degree of specificity for LPA; other lyso-glycerophospholipids, sphingosine 1-phosphate, and diacyl-glycerophospholipids did not activate FUS1::lacZ . LPA analogs including a cyclic phosphoester form and ether-linked forms of LPA activated FUS1::lacZ , although fatty acid chains of 6 and 10 carbons did not activate FUS1::lacZ , suggesting a role for the side chain in ligand binding or receptor activation. These results indicate that Edg-2 encodes a highly specific LPA receptor.
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