LPAR1/EDG-2 [B10]

The EDG (endothelial differentiation gene) family of GPC-receptors consists of eight family members (EDG1-8) that bind lysophospholipid (LPL) mediators either sphingosine-1-phosphate (SPP) or lysophosphatidic acid (LPA). EDG1, EDG3, EDG5 and EDG8 bind SPP with high affinity and EDG6 with low affinity. EDG2, EDG4 and EDG7 bind LPA preferentially. The EDG receptors couple to multiple G proteins to signal through Ras, MAP kinase, Rho, Phospholipase C or other tyrosine kinases, which lead to cell survival, growth, migration and differentiation. EDG2 or LPAR1, expressed in brain especially in white matter tract regions, interacts with RALA, ADRBK1 etc. In the absence of LPA, it can be found predominantly at the cell surface; whereas in the presence of LPA, it co-localizes with RALA in the endocytic vesicles. It is well established that platelets, certain inflammatory cells, nerve cells, endothelial cells, cancerous cells etc. are triggered to release LPA in autocrine/paracrine fashion with the induction of diverse biologic effects.