Homo- and hetero-dimerization of LPA/S1P receptors, OGR1 and GPR4.
G protein coupled receptors (GPCRs) form homo- and hetero-dimers or -oligomers, which are functionally important. Lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) are bioactive lysophopholipids involved in diverse biological processes. We have examined homo- and hetero-dimerization among three major LPA receptors (LPA(1-3)), three major S1P receptors (S1P(1-3)), as well as OGR1 and GPR4. Using LacZ complementation assays, we have shown that LPA receptors form homo- and hetero-dimers within the LPA receptor subgroup and hetero-dimers with other receptors (S1P(1-3) and GPR4). In addition, we have found that although GPR4 and OGR1 share more than 50% homology, GPR4 forms strong homo- and hetero-dimers with LPA and S1P receptors, but OGR1 forms very weak homo-dimer and relatively weak hetero-dimers with other receptors. Using chimeric receptors between GPR4 and OGR1, we have shown that different domains of GPR4 receptor are involved in its dimerization with different GPCRs and more than one domain may be involved in some of the complex formation. Our results suggest that when studying a signal transduction induced by a stimulus, not only is the expression and activation of its own receptor(s), but also the status of the interacting receptors should be taken into consideration.
Zaslavsky
Alexander
A
Department of Cancer Biology, The Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
Singh
Lisam Shanjukumar
LS
Tan
Haiyan
H
Ding
Huawen
H
Liang
Zicai
Z
Xu
Yan
Y
D019281:Dimerization; D008246:Lysophospholipids / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry*; D049368:Receptors, Lysophosphatidic Acid / Q000378:metabolism*; D049349:Receptors, Lysosphingolipid / Q000378:metabolism*
C091670:GPR4 protein, human; C486281:GPR68 protein, human; D008246:Lysophospholipids; D043562:Receptors, G-Protein-Coupled; D049368:Receptors, Lysophosphatidic Acid; D049349:Receptors, Lysosphingolipid; C032881:lysophosphatidic acid