乳酸脱氢酶A
福克斯O1
蛋白激酶B
细胞生物学
瓦博格效应
PI3K/AKT/mTOR通路
信号转导
生物
三磷酸腺苷
糖酵解
化学
激酶
效应器
磷酸肌醇3激酶
磷脂酰肌醇
癌症研究
生物化学
新陈代谢
作者
Ke Xu,Na Yin,Min Peng,Efstathios G. Stamatiades,Amy Shyu,Peng Li,Xian Zhang,H. Mytrang,Zhaoquan Wang,Kristelle J. Capistrano,Chun Chou,Andrew G. Levine,Alexander Y. Rudensky,Ming O. Li
标识
DOI:10.1101/2020.03.12.989707
摘要
Abstract Infection triggers clonal expansion and effector differentiation of microbial antigen-specific T cells in association with metabolic reprograming. Here, we show that the glycolytic enzyme lactate dehydrogenase A (LDHA) is induced in CD8 + T effector cells via phosphoinositide 3-kinase (PI3K)-dependent mechanisms. In turn, ablation of LDHA inhibits PI3K-dependent phosphorylation of Akt and its transcription factor target Foxo1, causing defective antimicrobial immunity. LDHA deficiency cripples cellular redox control and diminishes glycolytic adenosine triphosphate (ATP) production in effector T cells, resulting in attenuated PI3K signaling. Thus, nutrient metabolism and growth factor signaling are highly integrated processes with glycolytic ATP serving as a rheostat to gauge PI3K/Akt/Foxo1 signaling in T cell immunity control. Such a bioenergetics mechanism of signaling regulation implies a root cause for the century-old phenomenon of Warburg effect, and could guide development of novel therapeutics for infectious diseases and cancer. One Sentence Summary A PI3K and LDHA circuit enables T cell immunity
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