Zaslavsky Alexander, Singh Lisam Shanjukumar, Tan Haiyan, Ding Huawen, Liang Zicai, Xu Yan
Department of Cancer Biology, The Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
Biochim Biophys Acta. 2006 Oct;1761(10):1200-12. doi: 10.1016/j.bbalip.2006.08.011. Epub 2006 Aug 30.
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.
G蛋白偶联受体（GPCRs）可形成同二聚体、异二聚体或寡聚体，这些在功能上具有重要意义。溶血磷脂酸（LPA）和1-磷酸鞘氨醇（S1P）是参与多种生物学过程的生物活性溶血磷脂。我们研究了三种主要的LPA受体（LPA(1 - 3)）、三种主要的S1P受体（S1P(1 - 3)）以及OGR1和GPR4之间的同二聚化和异二聚化。使用LacZ互补分析，我们发现LPA受体在LPA受体亚组内形成同二聚体和异二聚体，并与其他受体（S1P(1 - 3)和GPR4）形成异二聚体。此外，我们发现尽管GPR4和OGR1有超过50%的同源性，但GPR4与LPA和S1P受体形成强同二聚体和异二聚体，而OGR1形成非常弱的同二聚体以及与其他受体形成相对较弱的异二聚体。通过构建GPR4和OGR1之间的嵌合受体，我们发现GPR4受体的不同结构域参与其与不同GPCR的二聚化，并且在某些复合物形成中可能涉及不止一个结构域。我们的结果表明，在研究由刺激诱导的信号转导时，不仅要考虑其自身受体的表达和激活，还应考虑相互作用受体的状态。
