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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-47741

Schläfli, P; Tröger, J; Eckhardt, K; Borter, E; Spielmann, P; Wenger, R H (2011). Substrate preference and phosphatidylinositol monophosphate inhibition of the catalytic domain of the PAS kinase PASKIN. FEBS Journal, 278(10):1757-1768.

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Abstract

The PAS domain serine/threonine kinase PASKIN, or PAS kinase, links energy flux and protein synthesis in yeast, regulates glycogen synthesis and protein translation in mammals, and might be involved in insulin regulation in the pancreas. According to the current model, binding of a putative ligand to the PAS domain disinhibits the kinase domain, leading to PASKIN autophosphorylation and increased kinase activity. Up to date, only synthetic but no endogenous PASKIN ligands have been reported. Here, we identified a number of novel PASKIN kinase targets, including ribosomal protein S6. Together with our previous identification of eukaryotic translation elongation factor eEF1A1, this suggests a role for PASKIN in the regulation of mammalian protein translation. While searching for endogenous PASKIN ligands, we found that various phospholipids can bind PASKIN and stimulate its autophosphorylation. Interestingly, strongest binding and autophosphorylation was achieved with monophosphorylated phosphatidylinositols. However, stimulated PASKIN autophosphorylation did not correlate with ribosomal protein S6 and eEF1A1 target phosphorylation. Whereas autophosphorylation was enhanced by monophosphorylated phosphatidylinositols, di- and triphosphorylated phosphatidylinositols inhibited autophosphorylation. In contrast, target phosphorylation was always inhibited, with highest efficiency of di- and tri-phosphorylated phosphatidylinositols. Since phosphatidylinositol monophosphates were found to interact with the kinase rather than with the PAS domain, these data suggest a multi-ligand regulation of PASKIN activity, including a still unknown PAS domain binding/activating ligand and kinase domain binding modulatory phosphatidylinositol phosphates.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Physiology
07 Faculty of Science > Institute of Physiology

04 Faculty of Medicine > Center for Integrative Human Physiology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Date:2011
Deposited On:24 Mar 2011 14:19
Last Modified:27 Nov 2013 22:54
Publisher:Wiley-Blackwell
ISSN:1742-464X
Additional Information:The definitive version is available at www.blackwell-synergy.com
Publisher DOI:10.1111/j.1742-4658.2011.08100.x
PubMed ID:21418524

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