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The PAS-domain kinase PASKIN: a new sensor in energy homeostasis

Journal

CELLULAR AND MOLECULAR LIFE SCIENCES
Volume 66, Issue 5, Pages 876-883

Publisher

SPRINGER BASEL AG
DOI: 10.1007/s00018-009-8699-0

Keywords

Diabetes mellitus; glucose tolerance; glycogen synthesis; insulin; metabolic syndrome; nitrogen fixation; protein translation; respiration

Funding

  1. Wolfermann-Nageli-Stiftung
  2. Baugarten Stiftung/Stiftung fur Wissenschaftliche Forschung an der Universitat Zurich
  3. Swiss National Science Foundation (SNF ) [3100AO-116047/1]

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The PAS domain kinase PASKIN, also termed PAS kinase or PASK, is an evolutionarily conserved potential sensor kinase related to the heme-based oxygen sensors of nitrogen-fixing bacteria. In yeast, the two PASKIN homologs link energy flux and protein synthesis following specific stress conditions. In mammals, PASKIN may regulate glycogen synthesis and protein translation. Paskin knock-out mice do not show any phenotype under standard animal husbandry conditions. Interestingly, these mice seem to be protected from the symptoms of the metabolic syndrome when fed a high-fat diet. Energy turnover might be increased in specific PASKIN-deficient cell types under distinct environmental conditions. According to the current model, binding of a putative ligand to the PAS domain disinhibits the kinase domain and activates PASKIN auto- and target phosphorylation. Future research needs to be conducted to elucidate the nature of the putative ligand and the molecular mechanisms of downstream signalling by PASKIN.

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