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Updated: Jul 22, 2026
11:13
Identification of Kinase-substrate Pairs Using High Throughput Screening
Published on: August 29, 2015
PAS kinase: an evolutionarily conserved PAS domain-regulated serine/threonine kinase.
J Rutter1, C H Michnoff, S M Harper
1Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9152, USA.
Summary
PAS kinase (PASK) is a novel mammalian protein kinase regulated by its PAS domains. Autophosphorylation and the N-terminal PAS domain control PASK activity, offering insights into eukaryotic signaling pathways.
Area of Science:
- Biochemistry
- Molecular Biology
- Cell Signaling
Background:
- PAS domains are crucial regulators of intracellular signaling pathways in response to stimuli.
- PAS domain-regulated histidine kinases are prevalent in prokaryotes but rare in eukaryotes.
- Mammals lack known PAS domain-regulated kinases, making PASK a unique discovery.
Purpose of the Study:
- To investigate the regulatory mechanisms of the evolutionarily conserved PAS kinase (PASK) in mammals.
- To determine if PASK represents the first mammalian PAS-regulated protein kinase.
- To elucidate the role of PAS domains in PASK's catalytic activity.
Main Methods:
- Analysis of PASK's amino acid sequence to identify functional domains (two PAS, one serine/threonine kinase).
- Investigating PASK activity regulation through autophosphorylation studies.
- Assessing the impact of PAS domain deletion and trans-complementation on enzyme activity.
Main Results:
- PASK activity is significantly enhanced by autophosphorylation at two threonine residues in the activation loop.
- The N-terminal PAS domain acts as a cis-regulator, inhibiting PASK catalytic activity.
- Removal of the PAS domain increases enzyme activity, while addition of the PAS-A domain in trans selectively inhibits PASK.
Conclusions:
- PASK is a eukaryotic signaling pathway regulated by PAS domains and autophosphorylation.
- These findings establish PASK as a potential model for studying PAS domain regulation in vitro.
- The discovery of PASK opens new avenues for understanding mammalian intracellular signaling.
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