Physiological roles of mitogen-activated-protein-kinase-activated p38-regulated/activated protein kinase

Mitogen-activated protein kinases(MAPKs)are a family of proteins that constitute signaling pathways involved in processes that control gene expression,cell division, cell survival,apoptosis,metabolism,differentiation and motility.The MAPK pathways can be divided into conventional and atypical MAPK pathways.The first group converts a signal into a cellular response through a relay of three consecutive phosphorylation events exerted by MAPK kinase kinases,MAPK kinase,and MAPK.Atypical MAPK pathways are not organized into this three-tiered cascade.MAPK that belongs to both conventional and atypical MAPK pathways can phosphorylate both non-protein kinase substrates and other protein kinases.The latter are referred to as MAPK-activated protein kinases.This review focuses on one such MAPK-activated protein kinase,MAPK-activated protein kinase 5(MK5)or p38-regulated/activated protein kinase(PRAK).This protein is highly conserved throughout the animal kingdom and seems to be the target of both conventional and atypical MAPK pathways.Recent findings on the regulation of the activity and subcellular localization,bona fide interaction partners and physiological roles of MK5/PRAK are discussed.

冬凌草甲素抑制结肠癌细胞HT-29的作用及其机制

目的探讨冬凌草甲素抑制结肠癌细胞HT-29的作用及其机制。方法浓度为1—50μmol／L的冬凌草甲素分别作用结肠癌细胞或转染小干扰RNA（siRNA）的结肠癌细胞，噻唑蓝（MTY）法观察冬凌草甲素对结肠癌细胞活力的影响，Western blot检测冬凌草甲素作用的HT-29细胞中腺苷酸活化蛋白激酶α（AMPKα）、磷酸化AMPKα（p-AMPKα）、乙酰辅酶A羧化酶（ACC）、磷酸化ACC（p-ACC）、磷酸化p53（p-p53）、磷酸化S6K（p-s6K）及磷酸化S6（p-S6）的表达。结果冬凌草甲素具有抑制结肠癌细胞活力的作用，其抑制作用呈时间剂量曲线，50μmol／L的冬凌草甲素作用HT-29细胞72h后的细胞活力最低，为21．6％。随着作用时间和剂量的增加，HT-29细胞P—AMPKot、p-ACC和p-p53蛋白表达逐渐增加，p-S6K及P—S6的蛋白表达减弱。转染AMPKotsiRNA的结肠癌细胞活力为（73．3±2．8）％，明显高于转染错义siRNA组的细胞活力[（19．5±1．2）％]，两组间差异有统计学意义（P〈0．05），p-AMPKα、p-ACC、AMPKα和p—p53蛋白表达强于转染错义siRNA组，而p—S6的蛋白表达弱于转染错义siRNA组。结论冬凌草甲索通过AMPKα活化通路抑制HT-29细胞活力。冬凌草甲素抑制结肠癌细胞活力与p-AMPKot、p-p53蛋白激活及p-S6K与p-S6的蛋白抑制相关，p53、S6可能是冬凌草甲素抑制结肠癌细胞p-AMPKα活化通路的下游蛋白。