Premium
Regulation of PASK function by mTOR signaling pathway
Author(s) -
Kikani Chintan K,
Rutter Jared P
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.758.15
Subject(s) - pi3k/akt/mtor pathway , phosphorylation , kinase , insulin resistance , microbiology and biotechnology , biology , effector , rptor , signal transduction , insulin , endocrinology
PAS domain containing serine/threonine kinase (PASK) is an evolutionary conserved protein kinase implicated in insulin resistance and type II diabetes. Specifically, we have shown a role for role for PASK in regulation hepatic lipogenesis pathways and insulin resistance using PASK knockout mice. It, however, remains unknown how PASK is regulated in cells and its downstream effectors. Here, we demonstrate that PASK is a nutrient responsive kinase. Serum and glucose stimulated the activity of PASK which was significantly suppressed by either rapamycin treatment or mTOR silencing by RNAi. In addition, the in vivo phosphorylation of PASK increases in response to serum and insulin treatment in an mTOR catalytic function dependent manner. Mutation of the phosphorylation sites to alanine suppresses serum stimulated phosphorylation and activation of PASK. Finally, we show that PASK physically associated with mTOR complex 1 in serum dependent manner, suggesting a direct role for mTOR complex 1 in regulating PASK function. Taken together, our findings provide the first evidence for the role of mTOR in regulating PASK activity and function in response to nutritional cues.