Mammalian PASKIN, a PAS-Serine/Threonine Kinase Related to Bacterial Oxygen Sensors

Höfer, Thomas; Spielmann, Patrick; Stengel, Petra; Stier, Bettina; Katschinski, Dörthe M.; Desbaillets, Isabelle; Gassmann, Max; Wenger, Roland H.

doi:10.1006/bbrc.2001.5840

Cited by 27 publications

(32 citation statements)

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“…An XhoI fragment of the 129Sv(ev) genomic phage clone P1, containing mouse Paskin exons 7 to 15, was subcloned into pBluescript KSPII (Stratagene), yielding the plasmid pP1X (10). pP1X was cleaved with SalI to remove exons 10 to 14, and a SalI fragment derived from pGT1.8Ires␤geo (kind gift of A. Smith, Edinburgh, United Kingdom) was inserted instead, resulting in the targeting vector pPKO.…”

Section: Methodsmentioning

confidence: 99%

“…Genomic DNA was isolated from ES cell cultures and tail biopsy specimens by using standard techniques (24). Southern blotting was performed as described previously (10). Briefly, genomic DNA was digested with Ecl136II and the Southern blots were hybridized to a radioactively labeled 582-bp XhoI-Ecl136II fragment derived from the overlapping phage clone P5 (10).…”

Section: Methodsmentioning

confidence: 99%

“…Total RNA isolation and analysis by Northern blotting was performed as described previously (20). Hybridization probes spanning the PAS or kinase domains of PASKIN were isolated from the mouse PASKIN cDNA 3Ј end (clone IMAGp998H022323) and the human PASKIN cDNA 5Ј end (clone HA0/203), respectively, as described before (10). The ␤-geo probe was isolated from the plasmid pGT1.8Ires␤geo.…”

Section: Methodsmentioning

confidence: 99%

“…Of note, the human PASKIN and mouse Paskin genes share a relatively small promoter region with PPP1R7 and Ppp1r7, respectively, suggesting coexpression of the two genes (10). PPP1R7/Ppp1r7 encodes for Sds22, the regulatory subunit 7 involved in target protein recognition of the serine/threonine protein phosphatase 1 (PP1) (2)(3)(4).…”

mentioning

confidence: 99%

“…Moreover, as might be expected for a sensory protein, PASKIN is ubiquitously expressed at rather low levels (10). In order to understand the physiological role of PASKIN in mammals, we targeted the mouse Paskin gene by homologous recombination.…”

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Targeted Disruption of the Mouse PAS Domain Serine/Threonine Kinase PASKIN

Katschinski

Marti

Wagner

et al. 2003

Molecular and Cellular Biology

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The PAS (Per-Arnt-Sim) domain is a widespread protein fold of environmental protein sensors involved in the perception of light intensity, oxygen partial pressure, redox potentials, and voltage (9,18,26,29). While most PAS proteins are known from the archaea, bacteria, and lower eukarya, relatively few sensor PAS proteins have been reported in mammalian species. Apart from the HERG voltage-dependent potassium channel (15), the mammalian PAS domain-containing proteins identified so far serve as heterodimerization interfaces of transcription factors involved in the xenobiotic response (25), adaptation to hypoxia (28), circadian rhythm generation (19), and possibly, carbon monoxide signaling (7).By database searches with the PAS sequence as a bait, we and others previously identified a novel mammalian PAS protein, termed PASKIN (10) or PAS kinase (22). The domain architecture of PASKIN resembles that of the oxygen sensor protein FixL from Rhizobium species which contains a hemebearing PAS domain and a histidine kinase domain that couples sensing to signaling (8). PASKIN contains two PAS domains, with higher sequence similarity to the FixL PAS domain than to any other known PAS domain, and a serine/threonine kinase domain related to AMP kinases. As known from FixL, the PAS A domain of PASKIN represses the kinase activity in cis. Following derepression, presumably by ligand-binding to the PAS domain, autophosphorylation in trans results in the switching on of the kinase domain of PASKIN (22).Of note, the human PASKIN and mouse Paskin genes share a relatively small promoter region with PPP1R7 and Ppp1r7, respectively, suggesting coexpression of the two genes (10). PPP1R7/Ppp1r7 encodes for Sds22, the regulatory subunit 7 involved in target protein recognition of the serine/threonine protein phosphatase 1 (PP1) (2-4). Thus, it is tempting to speculate that Sds22 directs PP1-mediated dephosphorylation of activated PASKIN, resulting in the switching off of the PASKIN kinase activity.The three-dimensional structure of the PASKIN PAS A domain has recently been resolved, and synthetic ligands binding to this domain were identified (1). Ligand binding as well as mutation of the PAS A domain result in the activation of the kinase domain. The synthetic ligands identified are structurally related to dioxin, known to bind to the PAS domain of the dioxin receptor. However, an endogenous ligand of PASKIN has not been identified so far. While the physiological function of mammalian PASKIN is unknown, important insights into the function of the two Saccharomyces cerevisiae homologs have recently been obtained (23). The yeast PASKIN homologs phosphorylate three translation factors and two enzymes involved in the regulation of glycogen and trehalose synthesis, thereby coordinately controlling translation and

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Targeted Disruption of the Mouse PAS Domain Serine/Threonine Kinase PASKIN

Katschinski

Marti

Wagner

et al. 2003

Molecular and Cellular Biology

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FARP2, HDLBP and PASK are downregulated in a patient with autism and 2q37.3 deletion syndrome

Felder

Radlwimmer

Benner

et al. 2009

American J of Med Genetics Pt A

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We describe a patient with autism and brachymetaphalangy, meeting criteria for 2q37 deletion syndrome (also called Albright Hereditary Osteodystrophy-like syndrome or Brachydactyly-Mental Retardation syndrome, OMIM 600430). Our molecular cytogenetic studies, including array comparative genomic hybridization (aCGH) and fluorescence in situ hybridization (FISH), define the extent of the de novo deletion to a 3.5 Mb region on 2q37.3. Although a number of reports of patients with 2q37 deletion syndrome have been published, it remains unclear if gene expression and/or translation are altered by the deletion, thus contributing to the observed phenotypes. To address this question, we selected several candidate genes for the neuropsychiatric and skeletal anomalies found in this patient (autism and brachymetaphalangy). The deleted region in 2q37.3 includes the FERM, RhoGEF and pleckstrin domain protein 2 (FARP2), glypican 1 (GPC1), vigilin (HDLBP), kinesin family member 1A (KIF1A) and proline-alanine-rich STE20-related kinase (PASK), all of which are involved in skeletal or neural differentiation processes. Expression analyses of these genes were performed using RNA from lymphoblastoid cell lines of the patient and his family members. Here we demonstrate that three of these genes, FARP2, HDLBP, and PASK, are considerably downregulated in the patient's cell line. We hypothesize that haploinsufficiency of these genes may have contributed to the patient's clinical phenotype.

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PAS kinase: A nutrient sensing regulator of glucose homeostasis

DeMille

Grose

2013

IUBMB Life

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Per-Arnt-Sim (PAS) kinase (PASK, PASKIN, and PSK) is a member of the group of nutrient sensing protein kinases. These protein kinases sense the energy or nutrient status of the cell and regulate cellular metabolism appropriately. PAS kinase responds to glucose availability and regulates glucose homeostasis in yeast, mice, and man. Despite this pivotal role, the molecular mechanisms of PAS kinase regulation and function are largely unknown. This review focuses on what is known about PAS kinase, including its conservation from yeast to man, identified substrates, associated phenotypes and role in metabolic disease.

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Mammalian PASKIN, a PAS-Serine/Threonine Kinase Related to Bacterial Oxygen Sensors

Cited by 27 publications

References 25 publications

Targeted Disruption of the Mouse PAS Domain Serine/Threonine Kinase PASKIN

Targeted Disruption of the Mouse PAS Domain Serine/Threonine Kinase PASKIN

FARP2, HDLBP and PASK are downregulated in a patient with autism and 2q37.3 deletion syndrome

PAS kinase: A nutrient sensing regulator of glucose homeostasis

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