期刊
MOLECULAR AND CELLULAR BIOLOGY
卷 32, 期 12, 页码 2268-2278出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/MCB.00063-12
关键词
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资金
- National Institutes of Health [F32CA1238252, P01 CA104838]
- Leukemia & Lymphoma Scholar award
The endoplasmic reticulum (ER) resident PKR-like kinase (PERK) is necessary for Akt activation in response to ER stress. We demonstrate that PERK harbors intrinsic lipid kinase, favoring diacylglycerol (DAG) as a substrate and generating phosphatidic acid (PA). This activity of PERK correlates with activation of mTOR and phosphorylation of Akt on Ser473. PERK lipid kinase activity is regulated in a phosphatidylinositol 3-kinase (PI3K) p85 alpha-dependent manner. Moreover, PERK activity is essential during adipocyte differentiation. Because PA and Akt regulate many cellular functions, including cellular survival, proliferation, migratory responses, and metabolic adaptation, our findings suggest that PERK has a more extensive role in insulin signaling, insulin resistance, obesity, and tumorigenesis than previously thought.
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