期刊
MOLECULAR CELL
卷 76, 期 6, 页码 857-+出版社
CELL PRESS
DOI: 10.1016/j.molcel.2019.09.007
关键词
-
资金
- NIH [CA140515, CA183594, CA174786]
- National Institutes of Health [K01 HG006699]
- Joel A. Katz Music Medicine Fund - T.J. Martell Foundation/Winship Cancer Institute
- CDMRP [793843, CA140515] Funding Source: Federal RePORTER
The oxidative pentose phosphate pathway (oxiPPP) contributes to cell metabolism through not only the production of metabolic intermediates and reductive NADPH but also inhibition of LKB1-AMPK signaling by ribulose-5-phosphate (Ru-5-P), the product of the third oxiPPP enzyme 6-phosphogluconate dehydrogenase (6PGD). However, we found that knockdown of glucose-6-phosphate dehydrogenase (G6PD), the first oxiPPP enzyme, did not affect AMPK activation despite decreased Ru-5-P and subsequent LKB1 activation, due to enhanced activity of PP2A, the upstream phosphatase of AMPK. In contrast, knockdown of 6PGD or 6-phosphog luconolactonase (PGLS), the second oxiPPP enzyme, reduced PP2A activity. Mechanistically, knockdown of G6PD or PGLS decreased or increased 6-phosphogluconolactone level, respectively, which enhanced the inhibitory phosphorylation of PP2A by Src. Furthermore, gamma-6-phosphogluconolactone, an oxiPPP byproduct with unknown function generated through intramolecular rearrangement of delta-6-phosphogluconolactone, the only substrate of PGLS, bound to Src and enhanced PP2A recruitment. Together, oxiPPP regulates AMPK homeostasis by balancing the opposing LKB1 and PP2A.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据