Immunity 2012,
PMID: 23142783
Gulen, Muhammet F; Bulek, Katarzyna; Xiao, Hui; Yu, Minjia; Gao, Ji; Sun, Lillian; Beurel, Eleonore; Kaidanovich-Beilin, Oksana; Fox, Paul L; DiCorleto, Paul E; Wang, Jian-an; Qin, Jun; Wald, David N; Woodgett, James R; Jope, Richard S; Carman, Julie; Dongre, Ashok; Li, Xiaoxia
Interleukin-1 (IL-1)-induced activation of the mTOR kinase pathway has major influences on Th17 cell survival, proliferation, and effector function. Via biochemical and genetic approaches, the kinases IKKi and GSK3α were identified as the critical intermediate signaling components for IL-1-induced AKT activation, which in turn activated mTOR. Although insulin-induced AKT activation is known to phosphorylate and inactivate GSK3α and GSK3β, we found that GSK3α but not GSK3β formed a constitutive complex to phosphorylate and suppress AKT activation, showing that a reverse action from GSK to AKT can take place. Upon IL-1 stimulation, IKKi was activated to mediate GSK3α phosphorylation at S21, thereby inactivating GSK3α to promote IL-1-induced AKT-mTOR activation. Thus, IKKi has a critical role in Th17 cell maintenance and/or proliferation through the GSK-AKT-mTOR pathway, implicating the potential of IKKi as a therapeutic target.
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Text Mining Data
AKT → IL-1: "
Via biochemical and genetic approaches, the kinases IKKi and GSK3a were identified as the critical intermediate signaling components for
IL-1 induced
AKT activation, which in turn activated mTOR
"
AKT → insulin: "
Although insulin induced AKT activation is known to phosphorylate and inactivate GSK3a and GSK3ß, we found that GSK3a but not GSK3ß formed a constitutive complex to phosphorylate and suppress AKT activation, showing that a reverse action from GSK to AKT can take place
"
AKT-mTOR → IL-1: "
Upon IL-1 stimulation, IKKi was activated to mediate GSK3a phosphorylation at S21, thereby inactivating GSK3a to promote IL-1 induced AKT-mTOR activation
"
AKT-mTOR → IL-1: "
Upon IL-1 stimulation, IKKi was activated to mediate GSK3a phosphorylation at S21, thereby inactivating GSK3a to promote IL-1 induced AKT-mTOR activation
"
Manually curated Databases
No curated data.