PAS kinase: An evolutionarily conserved PAS domain-regulated serine/threonine kinase

J. Rutter, C. H. Michnoff, S. M. Harper, K. H. Gardner, S. L. McKnight

Research output: Contribution to journalArticle

79 Scopus citations

Abstract

PAS domains regulate the function of many intracellular signaling pathways in response to both extrinsic and intrinsic stimuli. PAS domain-regulated histidine kinases are common in prokaryotes and control a wide range of fundamental physiological processes. Similarly regulated kinases are rare in eukaryotes and are to date completely absent in mammals. PAS kinase (PASK) is an evolutionarily conserved gene product present in yeast, flies, and mammals. The amino acid sequence of PASK specifies two PAS domains followed by a canonical serine/threonine kinase domain, indicating that it might represent the first mammalian PAS-regulated protein kinase. We present evidence that the activity of PASK is regulated by two mechanisms. Autophosphorylation at two threonine residues located within the activation loop significantly increases catalytic activity. We further demonstrate that the N-terminal PAS domain is a cis regulator of PASK catalytic activity. When the PAS domain-containing region is removed, enzyme activity is significantly increased, and supplementation of the purified PAS-A domain in trans selectively inhibits PASK catalytic activity. These studies define a eukaryotic signaling pathway suitable for studies of PAS domains in a purified in vitro setting.

Original languageEnglish (US)
Pages (from-to)8991-8996
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume98
Issue number16
DOIs
StatePublished - Jul 31 2001

ASJC Scopus subject areas

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