Endosomal colocalization of melanocortin-3 receptor and beta-arrestins in CAD cells with altered modification of AKT/PKB.
The melanocortin 3-receptor is involved in regulating energy metabolism, body fluid composition and inflammatory responses. Melanocortin receptors function by activating membrane bound adenylate cyclase. However, the literature reports indicate that some G protein coupled receptors (GPCRs) can also activate mitogen activated protein kinase (MAPK) or phosphoinositide 3 kinase (PI3K) signaling pathways consequent to their endocytosis. These studies were undertaken to evaluate the role of these pathways in MC3R signaling in brain-stem neuronal cells. Recruitment of arrestins is implicated in the activation of secondary pathways by GPCRs and our data shows the colocalization of either arrestin B1 or B2 with MC3R in endosomes. An alteration in PKB phosphorylation pattern was observed in MC3R expressing cells independent of agonist stimulation. MC3R transfectants exhibited increased proliferation rates and inhibition of PKB pathway with triciribine abrogated cell proliferation in both vector control and MC3R transfectants. PKB is constitutively active in proliferating CAD cells but could be further activated by culturing the cells in differentiation medium. These studies suggest that the AKT/PKB pathway plays an important role in the proliferation of CAD cells and suggest a link between MC3R and cell growth pathways that may involve the alteration of AKT/PKB signaling pathway.
Nyan
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DC
Department of Biology, Morgan State University, Baltimore, MD 21251, USA.
Anbazhagan
R
R
Hughes-Darden
C A
CA
Wachira
S J M
SJ
D000730:Androstadienes / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D019390:Arrestins / Q000096:biosynthesis* / Q000235:genetics; D015153:Blotting, Western; D001933:Brain Stem / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D011992:Endosomes / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D008856:Microscopy, Fluorescence; D051058:Oncogene Protein v-akt / Q000235:genetics* / Q000502:physiology; D010957:Plasmids / Q000235:genetics; D044104:Receptor, Melanocortin, Type 3 / Q000096:biosynthesis* / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000187:drug effects; D012263:Ribonucleosides / Q000494:pharmacology; D013778:Tetrazolium Salts; D013844:Thiazoles; D014162:Transfection; D025801:Ubiquitin / Q000494:pharmacology; D000077191:Wortmannin; D000071557:beta-Arrestins
D000730:Androstadienes; D000970:Antineoplastic Agents; D019390:Arrestins; D044104:Receptor, Melanocortin, Type 3; D043562:Receptors, G-Protein-Coupled; D012263:Ribonucleosides; D013778:Tetrazolium Salts; D013844:Thiazoles; D025801:Ubiquitin; D000071557:beta-Arrestins; C023764:triciribine; D051058:Oncogene Protein v-akt; C022616:thiazolyl blue; D000077191:Wortmannin