Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.1.1.6 (CAD)
 4,420 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The melanocortin-3 receptor, MC3-R, is abundant in the brain and is activated by gamma-2-melanocyte stimulating hormone (gamma-2-MSH). We have previously reported the translocation of protein kinase C (PKC) in spontaneous hypertensive rat (SHR) brain synaptosomes treated with gamma-2-MSH. In this study, the expression of PKA and the related PKB in SHR brain synaptosomes was analyzed. PKA was detected in total synaptosomal fractions but not in particulate fractions, whereas PKB was not detected in either fraction. We next tested the hypothesis that the PKC pathway is involved in MC3-R signaling in a neuronal, CAD, cell line. Mobilization of intracellular Ca2+ was analyzed by dual fluorescence imaging of Fura-2AM loaded MC3-R transfected cells. An increase in intracellular Ca2+ was observed upon treatment with gamma-2-MSH. A MC3-R-green fluorescent protein (GFP) fusion protein was expressed and shown to localize mainly to the plasma membrane in the soma and to neurites in differentiated CAD cells. Treatment with gamma-2-MSH led to a punctate appearance and co-immunoprecipitation of the receptor fusion protein with protein kinase C-gamma (PKC-gamma). Differentiation of some neuronal cells has been shown to be associated with changes in the expression levels of protein kinase C isoenzymes. Induction of CAD cell differentiation was associated with down-regulation of the atypical PKC-zeta and protein kinase B (PKB/Akt1), that was less pronounced in MC3-R transfected cells. However, the levels of classical PKC isozymes, PKC-alpha, PKC-gamma, and PKC-beta were unchanged. These studies therefore indicate a role for PKC isozymes in gamma-2-MSH/MC3-R receptor signaling and in neuronal cell differentiation.
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PMID:Evidence for the interaction of protein kinase C and melanocortin 3-receptor signaling pathways. 1290 38

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.
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PMID:Endosomal colocalization of melanocortin-3 receptor and beta-arrestins in CAD cells with altered modification of AKT/PKB. 1829 23