The paper:
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)
The finding:
Between 1996 and 2006, researchers identified four G protein-coupled receptors (GPCRs) as lysophosphatidic acid (LPA) receptors, LPA1-4. 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.
The significance:
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...
The follow-up:
Since publication, researchers have reconfirmed LPA4-5 to be "bona fide" LPA receptors, and proposed three additional LPA receptors that are homologous to LPA4-5.
In the clinic:
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 LPA1-3]," said Andrew Tager, which is important as researchers move forward in drug development.
| Mouse knock-out studies link LPA receptors to the following disorders | |
| Neuropathic pain | LPA1 |
| Fibrosis | LPA1 |
| Developmental disorders | LPA1-2 |
| Infertility | LPA3 |
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