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Differential regulation of a CLC anion channel by SPAK kinase ortholog-mediated multisite phosphorylation

, : Differential regulation of a CLC anion channel by SPAK kinase ortholog-mediated multisite phosphorylation. American Journal of Physiology. Cell Physiology 302(12): C1702-C1712

Shrinkage-induced inhibition of the Caenorhabditis elegans cell volume and cell cycle-dependent CLC anion channel CLH-3b occurs by concomitant phosphorylation of S742 and S747, which are located on a 175 amino acid linker domain between cystathionine-β-synthase 1 (CBS1) and CBS2. Phosphorylation is mediated by the SPAK kinase homolog GCK-3 and is mimicked by substituting serine residues with glutamate. Type 1 serine/threonine protein phosphatases mediate swelling-induced channel dephosphorylation. S742E/S747E double mutant channels are constitutively inactive and cannot be activated by cell swelling. S742E and S747E mutant channels were fully active in the absence of GCK-3 and were inactive when coexpressed with the kinase. Both channels responded to cell volume changes. However, the S747E mutant channel activated and inactivated in response to cell swelling and shrinkage, respectively, much more slowly than either wild-type or S742E mutant channels. Slower activation and inactivation of S747E was not due to altered rates of dephosphorylation or dephosphorylation-dependent conformational changes. GCK-3 binds to the 175 amino acid inter-CBS linker domain. Coexpression of wild-type CLH-3b and GCK-3 with either wild-type or S742E linkers gave rise to similar channel activity and regulation. In contrast, coexpression with the S747E linker greatly enhanced basal channel activity and increased the rate of shrinkage-induced channel inactivation. Our findings suggest the intriguing possibility that the phosphorylation state of S742 in S747E mutant channels modulates GCK-3/channel interaction and hence channel phosphorylation. These results provide a foundation for further detailed studies of the role of multisite phosphorylation in regulating CLH-3b and GCK-3 activity.


PMID: 22357738

DOI: 10.1152/ajpcell.00419.2011

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Azzi A.; Gargani G., 1987: Survey on cryptococcosis in italy characters of the isolated strains. During 20 months 17 cryptococcosis cases were recorded; 15 in A.I.D.S. patients, one in a leukemia, one in a diabetes case. Three of the A.I.D.S. were haemophilic, the others generally drug-addicts. Ten strains (eight from the present survey, plus...

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Cholette, C.; Payne, M.A.; Cornell, G.N.; Beal, J.M., 1954: Serum lipid levels following operation. Surgical Forum 5: 424-428

New, L.L.u, K.C.ouse, G., 1993: The yeast gene MSH3 defines a new class of eukaryotic MutS homologues. We have identified a gene in Saccharomyces cerevisiae, MSH3, whose predicted protein product shares extensive sequence similarity with bacterial proteins involved in DNA mismatch repair as well as with the predicted protein product of the Rep-3 ge...

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Jia,; Xu, J.H.; Li,; Yu,, 2003: Isolation of lipase producer and its performance in enantioselective hydrolysis of glycidyl butyrate. A racemic glycidyl butyrate resolving strain, preliminarily identified as a Rhizopus sp., had been isolated from soil. Its extracellular lipase was found to enantioselectively hydrolyze the (S)-enantiomer of the chiral ester, with optimal activiti...

Leibson, P.J.; Ting, A.T.; Bonnema, J.D.; Abraham, R.T., 1994: Fc receptor-initiated signal transduction during NK cell activation Regulatory roles for p21-ras and phosphatidylinositol 3-kinase. Natural Immunity 13(4): 215

Cohen, J., 1994: AIDS vaccines. Immune Response Corp.--take two. Science 264(5164): 1402-1402

Zabel'yan O.M.; Leshchinskii L.A., 1980: Comparative evaluation of the effectiveness of 2 drug combinations strophanthin and potassium orotate strophanthin and methyl uracil during circulatory insufficiency. Studies in patients (176) revealed a statistically reliable change in indices of central hemodynamics. Both drug combinations may be used during treatment of circulatory insufficiency, while the combination of strophanthin and methyluracil is more...