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J Biol Chem

Title:		Edg-2/Vzg-1 couples to the yeast pheromone response pathway selectively in response to lysophosphatidic acid
Author(s):		Erickson JR; Wu JJ; Goddard JG; Tigyi G; Kawanishi K; Tomei LD; Kiefer MC;
Address:		"LXR Biotechnology Inc., Richmond, California 94804, USA. jerickson@lxr.com"
Journal Title:		J Biol Chem
Year:		1998
Volume:		273
Issue:		3
Page Number:		1506 - 1510
DOI:		10.1074/jbc.273.3.1506
ISSN/ISBN:		0021-9258 (Print) 0021-9258 (Linking)
Abstract:		"We 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 alpha protein (the GPA1 gene product). This indicates that, in sst2 delta 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"
Keywords:		"Dose-Response Relationship, Drug Fungal Proteins/*metabolism GTP-Binding Proteins/metabolism Humans Lipoproteins/*metabolism Lysophospholipids/*pharmacology Pheromones/*metabolism Protein Binding Protein Conformation Receptors, Cell Surface/*metabolism *R;"
Notes:		"MedlineErickson, J R Wu, J J Goddard, J G Tigyi, G Kawanishi, K Tomei, L D Kiefer, M C eng 1998/01/27 J Biol Chem. 1998 Jan 16; 273(3):1506-10. doi: 10.1074/jbc.273.3.1506"