Melanocortin 5 receptor signaling and internalization: Role of MAPK/ERK pathway and beta-arrestins 1/2

• Type: Article in International Scientific Journal
• Date: 2012

Authors

Rodrigues, AR (Author) Other; Almeida, Henrique (Author) FMUP; Gouveia, Alexandra (Author) FCNAUP

Journal

Title: Molecular and Cellular Endocrinology

Vol. 361

Pages: 69-79

ISSN: 0303-7207

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 21 Citations

Scopus - 20 Citations

Other information

Authenticus ID: P-002-5CZ

DOI: 10.1016/j.mce.2012.03.011

Abstract (EN): 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 15 min, 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 11