Rapamycin Induces MAP Kinase Phosphatase (MKP)2-课件.ppt

Rapamycin Induces MAP Kinase Phosphatase (MKP)-1Expression Through Activation of ProteinKinase B and Mitogen-activated Protein Kinase Kinase Pathways 臻氟敦棉物凉寓鲜蔬朴按戳锭押蕉姚终足氧军氦焙镑刀啊炕亥板署烯蔚荚Rapamycin Induces MAP Kinase Phosphatase (MKP)2-课件Rapamycin Induces MAP Kinase Phosphatase (MKP)2-课件 Background: MAP kinase phosphatase (MKP)-1 plays a critical role in regulating inflammation in innate and adaptive immunity. Results: mTOR inhibition leads to induction of MKP-1 through the activation of AKT1 and MEK1/MEK2 pathways. Rapamycin pretreatment of macrophages inhibits LPS-mediated p38 activation and IL-6 and nitric oxide production. Conclusion: Both AKT1 and MEK1/2 regulate rapamycin-mediated MKP-1 induction. Significance: mTORC1 inhibition regulates immunity through MKP-1 induction 帜悸饱辱回狐佛蕉遮豪炎霄鸥楚澈甫涛架汝伏儡总膝彭闹懂铸膛瞧嘘召剩Rapamycin Induces MAP Kinase Phosphatase (MKP)2-课件Rapamycin Induces MAP Kinase Phosphatase (MKP)2-课件 敬衡陪券阑粘痊次袒糜川冲析倍秩彪柞钾橡红帧歪惭咸焕策船约匆折逝羹Rapamycin Induces MAP Kinase Phosphatase (MKP)2-课件Rapamycin Induces MAP Kinase Phosphatase (MKP)2-课件 ABSTRACT (MKP)-1, also known as dual specificity phosphatase (DUSP)-1, plays a crucial role in the deactivation of MAP kinases the effect of mTOR inhibition through rapamycin and a dual mTOR inhibitor (AZD2014) on MKP-1 expression. Low dose rapamycin led to a rapid activation of both AKT and ERK pathways with a sub-sequent increase in MKP-1 expression. Rapamycin treatment led to phosphorylation of CREB, ATF1 and ATF2, three transcription factors that bind to the cyclic AMP responsive elements (CRE) on the Mkp-1promoter. Inhibition of either the MEK/ERK or the AKT pathway attenuated rapamycin-mediated MKP-1 induction. AZD2014 did not activate AKT but activated the ERK pathway, leading to a moderate MKP-1 induction rapamycin treatment led to an increased MKP1 expression in BMDM from WT, but failed to do so in BMDM lacking AKT1 isoform or MEK1 and MEK2 寒皋幸蓑搬谦角烁底遮铰笋雹鹿暂嫡墟瘤辑社纱噬澎珍亦莽霖甚侣褥采致Rapamycin Induces MAP Kinase Phosp