A single receptor encoded by vzg-1/lpA1/edg-2 couples to G proteins and mediates multiple cellular responses to lysophosphatidic acid

A single receptor encoded by vzg-1/lp_A1/edg-2 couples to G proteins and mediates multiple cellular responses to lysophosphatidic acid

^*Department of Pharmacology, ^†Neurosciences Program, and ^‡Biomedical Sciences Program, School of Medicine, University of California at San Diego, La Jolla, CA 92093-0636

Communicated by Susan S. Taylor, University of California, San Diego, La Jolla, CA (received for review January 30, 1998)

Abstract

Extracellular lysophosphatidic acid (LPA) produces diverse cellular responses in many cell types. Recent reports of several molecularly distinct G protein-coupled receptors have raised the possibility that the responses to LPA stimulation could be mediated by the combination of several uni-functional receptors. To address this issue, we analyzed one receptor encoded by ventricular zone gene-1 (vzg-1) (also referred to as lp _A1/edg-2) by using heterologous expression in a neuronal and nonneuronal cell line. VZG-1 expression was necessary and sufficient in mediating multiple effects of LPA: [³H]-LPA binding, G protein activation, stress fiber formation, neurite retraction, serum response element activation, and increased DNA synthesis. These results demonstrate that a single receptor, encoded by vzg-1, can activate multiple LPA-dependent responses in cells from distinct tissue lineages.

Footnotes

↵ § To whom reprint requests should be addressed. e-mail: jchun{at}ucsd.edu.
ABBREVIATIONS:

vzg-1,

ventricular zone gene-1;

LPA,

lysophosphatidic acid;

PTX,

pertussis toxin;

SRE,

serum response element;

TRITC,

tetramethylrhodamine isothiocyanate;

CAT,

chloramphenicol acetyltransferase