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Targeting regulators of G protein signaling (RGS proteins) to enhance agonist specificity

机译:靶向G蛋白信号传导(RGS蛋白)的调节剂,以增强激动剂特异性

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Members of the diverse regulator of G protein signaling (RGS protein) family enhance the GTPase activity of G protein alpha subunits and speed their deactivation. Thus they negatively regulate signal transduction mediated by Gi-and Gq-coupled receptors. RGS proteins exhibit both tonic and regulated inhibition of agonist responses, differentially controlling the sensitivity of tissues depending on their post-translational modifications and expression levels. Reducing the activity of RGS proteins genetically or by means of chemical inhibitors can enhance G protein coupled receptor (GPCR) responses. RGS inhibitors present the novel possibility of enhancing agonist selectivity in a manner that depends on the signaling pathway employed or the tissue in which the receptor resides. To fully exploit this capability, more information will be needed about the expression of RGS proteins in different tissues and under distinct pathophysiological circumstances. Also, advances in the development of cell-permeable high affinity and selective inhibitors of specific RGS proteins will be needed. Finally, animal models illustrating the physiological functions of RGS proteins will be essential to predicting the actions in humans.
机译:G蛋白信号传导(RGS蛋白)的多种调节器的成员增强了G蛋白α亚基的GTP酶活性并加速了它们的失活。因此,它们负负调通过Gi-and GQ偶联受体介导的信号转导。 RGS蛋白表现出滋补和调节的激动剂反应抑制,差异地控制组织的敏感性,这取决于其翻译后修饰和表达水平。通过化学抑制剂减少RGS蛋白的活性或通过化学抑制剂可以增强G蛋白偶联受体(GPCR)反应。 RGS抑制剂呈现了以取决于所用信号通路的方式或受体所在的组织的方式提高激动剂选择性的新可能性。为了充分利用这种能力,将需要更多信息关于不同组织中的RGS蛋白质和在不同的病理生理环境下的表达。而且,需要进行细胞可渗透的高亲和力和选择性抑制剂的进展。最后,说明RGS蛋白的生理功能的动物模型对于预测人类的行为至关重要。

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