Apelin-APJ signaling in retinal angiogenesis.

The G protein–coupled receptor (GPCR) APJ (X-msr, angiotensin receptor like 1b) was cloned in several laboratories by homology screening, with the goal of identifying new members of this class of cell surface receptor.1 This gene attracted attention because of its sequence similarity to the important angiotensin II type 1 receptor and its highly restricted pattern of expression in endothelial cells. Five years later, this GPCR was deorphanized with cloning of the APJ-endogenous ligand apelin. Apelin was found to be synthesized as a 77-aa preproprotein and cleaved to a number of active peptides, including those of 36, 17, and 13 amino acids. Interestingly, apelin was also found to be highly expressed in endothelial cells.