糖皮质激素受体磷酸化及其生理病理意义

Glucocorticoid receptor phosphorylation:the pathophysiological significance

糖皮质激素(glucocorticoid,GC)具有重要的生理和药理作用,其作用主要通过GC受体(glucocorticoid receptor,GR)的介导而发挥。作为配体依赖性的转录调节因子,GR的活性除了受GC调节外,还受磷酸化的调节。GR分子,特别是在它的N端区存在多个磷酸化位点,能以激素依赖性或者非依赖性的方式被细胞特异性的激酶,如周期素依赖性蛋白激酶(CDKs)、糖原合成酶激酶3β(GSK3β)和丝裂原激活的蛋白激酶(MAPKs)等磷酸化。磷酸化调节GR的信号转导与转录活性等,并影响组织细胞对GC的反应性和参与疾病的发生发展。本文就GR磷酸化方面的研究进展及其生理病理意义作一综述。

Glucocorticoid （GC） has important physiological and pharmacological effects, which are mainly mediated by the GC receptor （GR）. As a ligand-dependent transcriptional factor, GR activity is regulated by phosphorylation as well as GC; it is subject to hormone-dependent and -independent phosphorylation on several serine and threonine residues, especially in the N terminus. The GR is phosphorylated by cell-specific kinases such as cyclin-dependent kinases （CDKs）, glycogen synthase kinase 3β （GSK313） and mitogen-activated protein kinases （MAPKs）. Phosphorylation regulates signaling and transcriptional activity of GR, thereby modulates the response of ceils to GC and may be involved in the development and progression of diseases. Here we reviewed the recent research on GR phosphorylation and its pathophysiological significance.