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

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...

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Bibliographic Details
Published in:Molecular and cellular endocrinology 2012-09, Vol.361 (1-2), p.69-79
Main Authors: Rodrigues, Adriana R, Almeida, Henrique, Gouveia, Alexandra M
Format: Article
Language:English
Subjects:
Activation
Affinity
Kinases
Pathways
Phosphorylation
Receptors
Recycling
Surface chemistry
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Summary: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 Gi-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.
ISSN:0303-7207
DOI:10.1016/j.mce.2012.03.011