Isolation and Expression of PASK, a Serine/Threonine Kinase, During Rat Embryonic Development, with Special Emphasis on the Pancreas

Miao, Ningning; Fung, Brenda; Sánchez, Ricardo; Lydon, John P.; Barker, Doug; Pang, Kevin

doi:10.1177/002215540004801009

Cited by 17 publications

(12 citation statements)

References 39 publications

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“…Consistent with their role in ion transport, SPAK and OSR1 expression increases in killifish opercular epithelium as the fish adapts from seawater to fresh water (35). Thus, modulation of ion transport seems to be a major function of the kinase and, not surprisingly, the highest levels of kinase expression are seen in the secretory cell in C. elegans (12) and in mouse secreting and absorbing epithelia (36,45,52). However, OSR1 and SPAK have also been shown to carry out additional functions, such as acting as intermediates in cell signaling.…”

mentioning

confidence: 74%

Characterization of SPAK and OSR1, Regulatory Kinases of the Na-K-2Cl Cotransporter

Gagnon

England

Delpire

2006

Molecular and Cellular Biology

152

135

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Our recent studies demonstrate that SPAK (Ste20p-related Proline Alanine-rich Kinase), in combination with WNK4 [With No lysine (K) kinase], phosphorylates and stimulates the Na-K-2Cl cotransporter (NKCC1), whereas catalytically inactive SPAK (K104R) fails to activate the cotransporter. The catalytic domain of SPAK contains an activation loop between the well-conserved DFG and APE motifs. We speculated that four threonine residues (T231, T236, T243, and T247) in the activation loop might be sites of phosphorylation and kinase activation; therefore, we mutated each residue into an alanine. In this report, we demonstrate that coexpression of SPAK (T243A) or SPAK (T247A) with WNK4 not only prevented, but robustly inhibited, cotransporter activity in NKCC1-injected Xenopus laevis oocytes. These activation loop mutations produced an effect similar to that of the SPAK (K104R) mutant. In vitro phosphorylation experiments demonstrate that both intramolecular autophosphorylation of SPAK and phosphorylation of NKCC1 are significantly stronger in the presence of Mn 2؉ rather than Mg 2؉ . We also show that SPAK activity is markedly inhibited by staurosporine and K252a, partially inhibited by N-ethylmaleimide and diamide, and unaffected by arsenite. OSR1, a kinase closely related to SPAK, exhibited similar kinase properties and similar functional activation of NKCC1 when coexpressed with WNK4.Cation-chloride cotransporters (e.g., Na-K-2Cl and K-Cl cotransporters) serve multiple fundamental functions in a wide variety of tissues and organs. These include influencing ion and fluid movements in secreting or reabsorbing epithelia, control of CNS excitability, and cell volume regulation, proliferation, and survival (for a review, see reference 19). On the basis of the observations that the cotransporters are phosphoproteins and that phosphatase inhibitors affect cotransport activity, it is generally agreed that cotransporter regulation is mainly mediated through phosphorylation-dephosphorylation mechanisms. Activity of NKCC1, for instance, correlates directly with the phosphorylation state of the protein (33). For the past 20 years, the identity of the kinase in question has remained elusive. We have recently shown direct interaction between cation-chloride cotransporter and two Ste20p-related serine/threonine kinases, SPAK and OSR1 (45).There are some 30 protein kinases identified in mammals related to the budding Saccharomyces cerevisiae sterile 20 protein kinase (Ste20p). In 1991, Dan et al. divided the mammalian Ste20p-like kinases into two subgroups: the p21-activated kinases (PAKs; two subfamilies), which are characterized by a carboxyl-terminal catalytic domain, and the germinal center kinases (GCKs; eight subfamilies), which have their catalytic domain located at the amino terminus (10). Most Ste20p-like kinases stimulate mitogen-activated protein kinase (MAPK) cascades and thus participate in the modulation of cell motility (7), cell growth (31), and apoptosis (23).The GCK6 subfamily comprises two kinases: SPAK/PASK (Ste...

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mentioning

confidence: 74%

Characterization of SPAK and OSR1, Regulatory Kinases of the Na-K-2Cl Cotransporter

Gagnon

England

Delpire

2006

Molecular and Cellular Biology

152

135

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“…In situ hybridization demonstrated SPAK expression in rat embryonic (E14–E15) choroid plexus, myocardium, mesonephron, and dorsal root ganglia. Distinct expression of SPAK was also observed in early pancreatic epithelium and developing gut tube (185). OSR1 mRNA expression was found in lung, kidney, colon, thymus, heart, liver, spleen, skeletal muscle, ovary, leukocyte, small intestine, testis, prostate, placenta, brain, and pancreas (276).…”

Section: The Gck-vi Subfamily: Ste20/sps-1 Related Proline Alanimentioning

confidence: 99%

Molecular Physiology of SPAK and OSR1: Two Ste20-Related Protein Kinases Regulating Ion Transport

Gagnon

Delpire

2012

Physiological Reviews

118

108

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SPAK (Ste20-related proline alanine rich kinase) and OSR1 (oxidative stress responsive kinase) are members of the germinal center kinase VI sub-family of the mammalian Ste20 (Sterile20)-related protein kinase family. Although there are 30 enzymes in this protein kinase family, their conservation across the fungi, plant and animal kingdom confirms their evolutionary importance. Already, a large volume of work has accumulated on the tissue distribution, binding partners, signaling cascades, and physiological roles of mammalian SPAK and OSR1 in multiple organ systems. After reviewing this basic information, we will examine newer studies that demonstrate the pathophysiological consequences to SPAK and/or OSR1 disruption, discuss the development and analysis of genetically-engineered mouse models, and address the possible role these serine/threonine kinases might have in cancer proliferation and migration.

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“…A first hint for another kind of functional relationship between FixL and PASKIN was provided by the group of S. L. McKnight, J. Rutter and colleagues who cloned human PASKIN and alternatively termed it PAS kinase or PASK [17]. However, since this name had been in use before for an unrelated kinase [18,19] [20]. Thus, it was tempting to speculate that PASKIN binds (so far unknown) organic ligands, increases its kinase activity by autophosphorylation and signals to (so far unknown) downstream phosphoproteins.…”

Section: The Pas Domain Of Paskin Inhibits Serine/threonine Kinase Domentioning

confidence: 99%

The PAS-domain kinase PASKIN: a new sensor in energy homeostasis

Schläfli

Borter

Spielmann

et al. 2009

Cell. Mol. Life Sci.

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The PAS domain kinase PASKIN, also termed PAS kinase or PASK, is an evolutionarily conserved potential sensor kinase related to the heme-based oxygen sensors of nitrogen-fixing bacteria. In yeast, the two PASKIN homologs link energy flux and protein synthesis following specific stress conditions. In mammals, PASKIN may regulate glycogen synthesis and protein translation. Paskin knock-out mice do not show any phenotype under standard animal husbandry conditions. Interestingly, these mice seem to be protected from the symptoms of the metabolic syndrome when fed a high-fat diet. Energy turnover might be increased in specific PASKIN-deficient cell types under distinct environmental conditions. According to the current model, binding of a putative ligand to the PAS domain disinhibits the kinase domain and activates PASKIN auto- and target phosphorylation. Future research needs to be conducted to elucidate the nature of the putative ligand and the molecular mechanisms of downstream signalling by PASKIN.

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Isolation and Expression of PASK, a Serine/Threonine Kinase, During Rat Embryonic Development, with Special Emphasis on the Pancreas

Cited by 17 publications

References 39 publications

Characterization of SPAK and OSR1, Regulatory Kinases of the Na-K-2Cl Cotransporter

Characterization of SPAK and OSR1, Regulatory Kinases of the Na-K-2Cl Cotransporter

Molecular Physiology of SPAK and OSR1: Two Ste20-Related Protein Kinases Regulating Ion Transport

The PAS-domain kinase PASKIN: a new sensor in energy homeostasis

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