| First Author | Rourke JL | Year | 2015 |
| Journal | Mol Cell Endocrinol | Volume | 417 |
| Pages | 36-51 | PubMed ID | 26363224 |
| Mgi Jnum | J:236145 | Mgi Id | MGI:5804766 |
| Doi | 10.1016/j.mce.2015.09.002 | Citation | Rourke JL, et al. (2015) CMKLR1 and GPR1 mediate chemerin signaling through the RhoA/ROCK pathway. Mol Cell Endocrinol 417:36-51 |
| abstractText | Chemerin is an adipose-derived hormone that regulates immunity and energy homesotasis. To date, all known chemerin functions have been attributed to activation of the G protein-coupled receptor chemokine-like receptor-1 (CMKLR1). Chemerin is also the only known ligand for a second receptor, G protein-coupled receptor-1 (GPR1), whose signaling and function remains unknown. This study investigated the in vitro signal transduction mechanisms of CMKLR1 and GPR1 using a panel of luciferase-reporters and pathway-specific inhibitors. Herein we report the novel finding that chemerin signals through a RhoA and rho-associated protein kinase (ROCK)-dependent pathway for activation of the transcriptional regulator serum-response factor (SRF). Despite similarities in RhoA/ROCK, Galphai/o, and MAPK signaling, we also demonstrate species-specific and receptor-dependent variations in GPR1 and CMKLR1 signaling and expression of the SRF target genes EGR1, FOS and VCL. Moreover, we demonstrate that signaling through p38, Galphai/o, RhoA, and ROCK is required for chemerin-mediated chemotaxis of L1.2 lymphocytes and AGS gastric adenocarcinoma cells. These results provide, to our knowledge, the first empirical evidence that GPR1 is a functional chemerin receptor and identify RhoA/SRF as a novel chemerin-signaling axis via both CMKLR1 and GPR1. |
