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Am J Physiol Cell Physiol
2012 Dec 01;30311:C1198-205. doi: 10.1152/ajpcell.00284.2012.
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Calcium-binding protein 39 facilitates molecular interaction between Ste20p proline alanine-rich kinase and oxidative stress response 1 monomers.
Ponce-Coria J
,
Gagnon KB
,
Delpire E
.
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X-ray crystallography of the catalytic domain of oxidative stress response 1 (OSR1) has provided evidence for dimerization and domain swapping. However, the functional significance of dimer formation or domain swapping has yet to be addressed. In this study, we used nine glutamine residues to link the carboxyl end of one SPAK (related Ste20 kinase) monomer to the amino end of another SPAK monomer to assess the role of kinase monomers versus dimers in Na-K-2Cl cotransporter 1 (NKCC1) activation. Transport studies in Xenopus laevis oocytes show that forcing dimerization of two wild-type SPAK molecules results in cotransporter activation when calcium-binding protein 39 (Cab39) is coexpressed, indicating that the presence of Cab39 can bypass the upstream phosphorylation requirement of SPAK normally associated with kinase activation. We determined that monomers are the functional units of the kinase as concatamers consisting of an active and various inactive monomers were still functional. Furthermore, we found that two different nonfunctional SPAK mutants could be linked together in a concatamer and activated, presumably by domain swapping, indicating that dimerization and domain swapping are both important components of kinase activation. Finally, we demonstrate rescue of a nonfunctional SPAK mutant by domain swapping with wild-type OSR1, indicating that heterodimers of the two Ste20-related kinases are possible and therefore potentially relevant to the regulation of NKCC1 activity.
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Boudeau,
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Choe,
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Delpire,
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2008,
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Delpire,
The mammalian family of sterile 20p-like protein kinases.
2009,
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Delpire,
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2011,
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,
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Delpire,
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,
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Filippi,
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Gagnon,
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,
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Gagnon,
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2006,
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,
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Gagnon,
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2007,
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,
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Gagnon,
On the substrate recognition and negative regulation of SPAK, a kinase modulating Na+-K+-2Cl- cotransport activity.
2010,
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,
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Gagnon,
Functional insights into the activation mechanism of Ste20-related kinases.
2011,
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,
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Gamba,
Primary structure and functional expression of a cDNA encoding the thiazide-sensitive, electroneutral sodium-chloride cotransporter.
1993,
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,
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Geng,
The Ste20 kinases Ste20-related proline-alanine-rich kinase and oxidative-stress response 1 regulate NKCC1 function in sensory neurons.
2009,
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Grimm,
SPAK isoforms and OSR1 regulate sodium-chloride co-transporters in a nephron-specific manner.
2012,
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Lee,
Crystal structure of domain-swapped STE20 OSR1 kinase domain.
2009,
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Lin,
Impaired phosphorylation of Na(+)-K(+)-2Cl(-) cotransporter by oxidative stress-responsive kinase-1 deficiency manifests hypotension and Bartter-like syndrome.
2011,
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Liu,
3D domain swapping: as domains continue to swap.
2002,
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McCormick,
A SPAK isoform switch modulates renal salt transport and blood pressure.
2011,
Pubmed
Moriguchi,
WNK1 regulates phosphorylation of cation-chloride-coupled cotransporters via the STE20-related kinases, SPAK and OSR1.
2005,
Pubmed
Nolen,
Regulation of protein kinases; controlling activity through activation segment conformation.
2004,
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Oliver,
Trans-activation of the DNA-damage signalling protein kinase Chk2 by T-loop exchange.
2006,
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Pacheco-Alvarez,
The Na+:Cl- cotransporter is activated and phosphorylated at the amino-terminal domain upon intracellular chloride depletion.
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,
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Piechotta,
Characterization of the interaction of the stress kinase SPAK with the Na+-K+-2Cl- cotransporter in the nervous system: evidence for a scaffolding role of the kinase.
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,
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Piechotta,
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Pike,
Activation segment dimerization: a mechanism for kinase autophosphorylation of non-consensus sites.
2008,
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Rafiqi,
Role of the WNK-activated SPAK kinase in regulating blood pressure.
2010,
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Villa,
Structure of the OSR1 kinase, a hypertension drug target.
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Vitari,
The WNK1 and WNK4 protein kinases that are mutated in Gordon's hypertension syndrome phosphorylate and activate SPAK and OSR1 protein kinases.
2005,
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Wilson,
Molecular pathogenesis of inherited hypertension with hyperkalemia: the Na-Cl cotransporter is inhibited by wild-type but not mutant WNK4.
2003,
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,
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Yang,
Crystal structure of a cAMP-dependent protein kinase mutant at 1.26A: new insights into the catalytic mechanism.
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Yang,
SPAK-knockout mice manifest Gitelman syndrome and impaired vasoconstriction.
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Zhou,
WNK4 inhibits NCC protein expression through MAPK ERK1/2 signaling pathway.
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