Per-Arnt-Sim Kinase (PASK) is an evolutionarily-conserved nutrient-responsive protein kinase that regulates lipid and glucose metabolism, mitochondrial respiration, phosphorylation, and gene expression. Recent data suggests that mammalian PAS kinase is involved in glucose metabolism and acts on pancreatic islet α/β cells and glycogen synthase (GS), affecting insulin secretion and blood glucose levels. In addition, PASK knockout mice (PASK-/-) are protected from obesity, liver triglyceride accumulation, and insulin resistance when fed a high-fat diet, implying that PASK may be a new target for metabolic syndrome (MetS) treatment as well as the cellular nutrients and energy sensors-adenosine monophosphate (AMP)-activated protein kinase (AMPK) and the targets of rapamycin (m-TOR). In this review, we will briefly summarize the regulation of PASK on mammalian glucose and lipid metabolism and its possible mechanism, and further explore the potential targets for MetS therapy.
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http://dx.doi.org/10.3390/nu7095347 | DOI Listing |
Newborn (Clarksville)
March 2024
Global Newborn Society, Clarksville Maryland, United States of America.
bioRxiv
June 2024
Department of Biology, University of Kentucky, Lexington, Kentucky 40502, USA.
The Per-Arnt-Sim (PAS) domains are characterized by diverse sequences and feature tandemly arranged PAS and PAS-associated C-terminal (PAC) motifs that fold seamlessly to generate the metabolite-sensing PAS domain. Here, using evolutionary scale sequence, domain mapping, and deep learning-based protein structure analysis, we deconstructed the sequence-structure relationship to unearth a novel example of signal-regulated assembly of PAS and PAC subdomains in metazoan PAS domain-regulated kinase (PASK). By comparing protein sequence, domain architecture, and computational protein models between fish, bird, and mammalian PASK orthologs, we propose the existence of previously unrecognized third PAS domain of PASK (PAS-C) formed through long-range intramolecular interactions between the N-terminal PAS fold and the C-terminal PAC fold.
View Article and Find Full Text PDFJ Biol Chem
May 2024
Departments of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada. Electronic address:
Histidine kinases are key bacterial sensors that recognize diverse environmental stimuli. While mechanisms of phosphorylation and phosphotransfer by cytoplasmic kinase domains are relatively well-characterized, the ways in which extracytoplasmic sensor domains regulate activation remain mysterious. The Cpx envelope stress response is a conserved Gram-negative two-component system which is controlled by the sensor kinase CpxA.
View Article and Find Full Text PDFBiosci Biotechnol Biochem
February 2024
Department of Bioscience and Biotechnology, Fukui Prefectural University, Fukui, Japan.
We have previously isolated the Gram-positive chitin-degrading bacterium Paenibacillus sp. str. FPU-7.
View Article and Find Full Text PDFChem Biol Drug Des
January 2024
School of Medicine, Hangzhou City University, Hangzhou, China.
Jasminoidin (JAS) can alleviate ischemic stroke (IS) injury, but its molecular mechanism remains undefined. The polarization of microglia affects IS process. This research is powered to probe whether the molecular mechanism of JAS for IS treatment is coupled with microglia polarization.
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