Please use this identifier to cite or link to this item: https://hdl.handle.net/10216/93436
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dc.creatorRodrigues, AR
dc.creatorPignatelli, D
dc.creatorAlmeida, Henrique
dc.creatorGouveia, Alexandra
dc.date.accessioned2022-09-08T05:35:37Z-
dc.date.available2022-09-08T05:35:37Z-
dc.date.issued2009
dc.identifier.issn0303-7207
dc.identifier.othersigarra:47289
dc.identifier.urihttps://hdl.handle.net/10216/93436-
dc.description.abstractMelanocortin 5 receptor (MC5R) is a G protein coupled receptor (GPCR) with high affinity for alpha-melanocyte-stimulating hormone (alpha-MSH). To unravel some of the downstream cell-signaling pathways activated by this receptor, HEK293 cells were transiently and stably transfected with a vector encoding green fluorescent protein (GFP)-tagged MC5R. In these cells the receptor was correctly addressed to the cell Surface and was functional, as shown by the MC5R-induced formation of intracellular cAMP. In fact, the MC5R agonist alpha-MSH induced a 10- or 16-fold increase (transient or stable cells, respectively) above the cAMP levels found in unstimulated cells. Moreover, in cells stably expressing MC5R-GFP, a-MSH promoted ERK1/2 phosphorylation in a dose-dependent manner (EC50 = 7.3 nM) with the maximal effect occurring after 5 min of agonist incubation. The signaling pathway conveyed through ERK1/2 is not linked to cAMP, since the phosphorylation of these kinases is unchanged by the inhibition of adenylyl cyclase. Also, ERK1/2 activation is not significantly affected by protein kinase A (PKA), protein kinase C (PKC) and protein kinase B or Akt (Akt/PKB) specific inhibitors. However, alpha-MSH-induced ERK1/2 activation is abolished by the phosphatidylinositol 3-kinase (PI3K) inhibitors wortmannin and LY294002. Altogether, these findings demonstrate that MC5R signals through a PIA-regulated Akt-independent pathway leading to downstream activation of ERK1/2. The involvement of these MAPK suggests that MC5R could be implicated in cellular proliferation or differentiation mechanisms.
dc.language.isoeng
dc.rightsrestrictedAccess
dc.subjectCiências da Saúde, Outras ciências médicas
dc.subjectHealth sciences, Other medical sciences
dc.titleMelanocortin 5 receptor activates ERK1/2 through a PI3K-regulated signaling mechanism
dc.typeArtigo em Revista Científica Internacional
dc.contributor.uportoFaculdade de Ciências da Nutrição e Alimentação
dc.contributor.uportoFaculdade de Medicina
dc.identifier.doi10.1016/j.mce.2009.01.014
dc.identifier.authenticusP-003-K4Q
dc.subject.fosCiências médicas e da saúde::Outras ciências médicas
dc.subject.fosMedical and Health sciences::Other medical sciences
Appears in Collections:FCNAUP - Artigo em Revista Científica Internacional
FMUP - Artigo em Revista Científica Internacional

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