| First Author | Rodrigues AR | Year | 2012 |
| Journal | Mol Cell Endocrinol | Volume | 361 |
| Issue | 1-2 | Pages | 69-79 |
| PubMed ID | 22871966 | Mgi Jnum | J:189654 |
| Mgi Id | MGI:5446818 | Doi | 10.1016/j.mce.2012.03.011 |
| Citation | Rodrigues AR, et al. (2012) Melanocortin 5 receptor signaling and internalization: role of MAPK/ERK pathway and beta-arrestins 1/2. Mol Cell Endocrinol 361(1-2):69-79 |
| abstractText | The Melanocortin 5 receptor (MC5R) is a G-protein coupled receptor (GPCR) that exhibits high affinity for alpha-MSH. Here we present evidence for MC5R-GFP internalization and subsequent recycling to cell surface, in alpha-MSH-stimulated HeLa cells. This melanocortin induces a biphasic activation of ERK1/2 with an early peak at 15min, a G(i)-protein driven, beta-arrestins 1/2 independent process, and a late sustained activation that is regulated by beta-arrestins 1/2. ERK1/2 lead to downstream phosphorylation of 90-kDa ribosomal S6 kinases (p90RSK) and mitogen- and stress-activated protein kinase 1 (MSK1). Only a small fraction (10%) of phosphorylated p90RSK and ERK1/2 translocates to the nucleus inducing c-Fos expression. alpha-MSH also activates CREB through cAMP/PKA pathway. In 3T3-L1 adipocytes, where MC5R is endogenously expressed, alpha-MSH also induces phosphorylation and cytosolic retention of the same signaling molecules. These findings provide new evidence on the signaling mechanisms underlying MC5R biological response to alpha-MSH. |
