It’s been reported that activation of prostaglandin E receptor regulates cell proliferation by activating AKT PKB by means of recruitment of ARRB and our success demonstrate considerable colocalization of MCR with ARRB. Alternatively, MCR may well regulate the dephosphorylation of AKT PKB. This later likelihood is much more attractive because the band that is definitely decreased in MCR expressing cells cross reacts with anti phospho AKT antibodies and its regarded that AKT is topic to dephosphorylation by protein phosphatase A . MCR is coupled to the cAMP PKA pathway and PKA is identified to activate PPA by means of phosphorylation . This mechanism is thought to underlie some physiological results of cAMP elevation as activated PPA can in flip dephosphorylate dopamine and cAMP regulated phosphoprotein . Dephosphorylated DARPP binds and sequesters the broad spectrum phosphatase PP thereby primary to enhanced phosphorylation of many cellular proteins . Other workers have reported that AKT PKB ubiquitylation and subsequent proteasomal degradation is a vital mechanism for identifying neuronal polarity .
Protein phosphorylation is a vital stage preceding ubiquitylation and our westerns unveiled a greater molecular species that cross reacted with anti phospho AKT antibody . Moreover, induction of CAD cell differentiation was accompanied by greater SP600125 AKT PKB phosphorylation . Immunoprecipitation immunoblot confirmed that AKT PKB is ubiquitylated in these cells and this perhaps accounts for that heterogeneity in banding patterns. As a result of the prominent position played by the PIK AKT signaling pathway in cell survival, we carried out cell development scientific studies on MCR transfectants and control cells. MCR transfectants displayed increased cell growth as assessed by MTT reduction assay . Even further, triciribine inhibited the proliferation of CAD cells thereby implicating the AKT pathway in CAD cell survival as this compound is recognized to selectively inhibit the proliferation of AKT transformed cells .
GPCRs modulate cell growth and proliferation by activating distinct mechanisms which include the PIK PKB pathway . Provided that MCR continues to be shown to activate ERK by way of the PIK pathway , its conceivable the alterations in AKT PKB phosphorylation patterns observed in these studies arise from activation of this pathway. In vivo, melanocortin Screening Libraries peptides are concerned within the proliferation and upkeep of melanocytes and adrenal cells, when deletion of POMC results in the growth of pituitary tumors in mice suggesting an important role for melanocortin receptors in cell growth and proliferation . Additional, a evaluate of MCR expression patterns through the gene expression omnibus, GEO database , signifies that MCR is extremely expressed in some tumors together with clear cell sarcoma of your kidney, breast tumors and metastatic pituitary tumors but absent in others.