PERK utilizes intrinsic lipid kinase activity to generate phosphatidic acid, mediate Akt activation, and promote adipocyte differentiation. Mol Cell Biol 2012 Jun;32(12):2268-78
Date
04/12/2012Pubmed ID
22493067Pubmed Central ID
PMC3372262DOI
10.1128/MCB.00063-12Scopus ID
2-s2.0-84864003561 (requires institutional sign-in at Scopus site) 89 CitationsAbstract
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) p85α-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.
Author List
Bobrovnikova-Marjon E, Pytel D, Riese MJ, Vaites LP, Singh N, Koretzky GA, Witze ES, Diehl JAMESH terms used to index this publication - Major topics in bold
AdipocytesAnimals
Cell Differentiation
Cell Line
Endoplasmic Reticulum
Endoplasmic Reticulum Stress
Enzyme Activation
Lipid Metabolism
Mice
Phosphatidic Acids
Phosphatidylinositol 3-Kinases
Phosphorylation
Proto-Oncogene Proteins c-akt
Signal Transduction
TOR Serine-Threonine Kinases
eIF-2 Kinase
