LPA leaps

Journal of Biological Chemistry, vol. 280, issue 41, 10/14/05, courtesy of Yuko Fujiwara, University of Tennessee Cancer Institute, Memphis, TN

J. Chun et al., "GPR92 as a new G(12/13)- and G(q)-coupled lysophosphatidic acid receptor that increases cAMP, LPA(5)," J Biol Chem, 281:23589-97, 2006. (Cited in 75 papers)

Between 1996 and 2006, researchers identified four G protein-coupled receptors (GPCRs) as lysophosphatidic acid (LPA) receptors, LPA_1-4. Jerold Chun's team at The Scripps Research Institute screened collections of orphan GPCRs, using reverse transfection to measure LPA-dependent cellular morphological changes, and identified a potential LPA receptor. Through heterologous expression and measuring downstream signaling, Chun identified GPR92 as a new receptor, LPA₅.

Sequencing revealed that LPA₅ shared homology with LPA₄, but not the other three, suggesting there were at least two distinct families of LPA receptors. "People are now looking more seriously at the possibility of other non-homologous [LPA] receptors, mediating a variety of physiological and pathophysiological actions," says Chun, suggesting the two subfamilies mediate different cellular responses.

Since publication, researchers have reconfirmed LPA_4-5 to be "bona fide" LPA receptors, and proposed three additional LPA receptors that are homologous to LPA_4-5.

An LPA₁ and LPA₃ receptor antagonist compound is in preclinical trials for the treatment in local as well as metastatic cancer. "From this study we now know LPA₄ and LPA₅ mediate LPA activities differently [than LPA_1-3]," said Andrew Tager, which is important as researchers move forward in drug development.