Document Detail

Calcium-binding protein 39 facilitates molecular interaction between Ste20p proline alanine-rich kinase and oxidative stress response 1 monomers.
MedLine Citation:
PMID:  23034389     Owner:  NLM     Status:  MEDLINE    
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.
José Ponce-Coria; Kenneth B Gagnon; Eric Delpire
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-10-03
Journal Detail:
Title:  American journal of physiology. Cell physiology     Volume:  303     ISSN:  1522-1563     ISO Abbreviation:  Am. J. Physiol., Cell Physiol.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-03     Completed Date:  2013-02-11     Revised Date:  2013-12-04    
Medline Journal Info:
Nlm Unique ID:  100901225     Medline TA:  Am J Physiol Cell Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  C1198-205     Citation Subset:  IM    
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MeSH Terms
Amino Acid Sequence
Biological Transport
Calcium-Binding Proteins / chemistry,  metabolism*
Crystallography, X-Ray
Glutamine / chemistry
Molecular Sequence Data
Protein Binding
Protein Interaction Domains and Motifs
Protein Structure, Tertiary
Protein-Serine-Threonine Kinases / chemistry,  metabolism*
Sodium-Potassium-Chloride Symporters / chemistry,  metabolism
Solute Carrier Family 12, Member 2
Xenopus laevis
Grant Support
Reg. No./Substance:
0/Calcium-Binding Proteins; 0/Mo25 protein, human; 0/SLC12A2 protein, human; 0/Sodium-Potassium-Chloride Symporters; 0/Solute Carrier Family 12, Member 2; 0RH81L854J/Glutamine; EC 2.7.1.-/OXSR1 protein, human; EC Kinases; EC protein, human

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