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SIK1 is part of a cell sodium-sensing network that regulates active sodium transport through a calcium-dependent process.

Authors: Sjostrom, M  Stenstrom, K  Eneling, K  Zwiller, J  Katz, AI  Takemori, H  Bertorello, AM 
Citation: Sjostrom M, etal., Proc Natl Acad Sci U S A. 2007 Oct 23;104(43):16922-7. Epub 2007 Oct 15.
Pubmed: (View Article at PubMed) PMID:17939993
DOI: Full-text: DOI:10.1073/pnas.0706838104

In mammalian cells, active sodium transport and its derived functions (e.g., plasma membrane potential) are dictated by the activity of the Na(+),K(+)-ATPase (NK), whose regulation is essential for maintaining cell volume and composition, as well as other vital cell functions. Here we report the existence of a salt-inducible kinase-1 (SIK1) that associates constitutively with the NK regulatory complex and is responsible for increases in its catalytic activity following small elevations in intracellular sodium concentrations. Increases in intracellular sodium are paralleled by elevations in intracellular calcium through the reversible Na(+)/Ca(2+) exchanger, leading to the activation of SIK1 (Thr-322 phosphorylation) by a calcium calmodulin-dependent kinase. Activation of SIK1 results in the dephosphorylation of the NK alpha-subunit and an increase in its catalytic activity. A protein phosphatase 2A/phosphatase methylesterase-1 (PME-1) complex, which constitutively associates with the NK alpha-subunit, is activated by SIK1 through phosphorylation of PME-1 and its dissociation from the complex. These observations illustrate the existence of a distinct intracellular signaling network, with SIK1 at its core, which is triggered by a monovalent cation (Na(+)) and links sodium permeability to its active transport.


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RGD Object Information
RGD ID: 8554378
Created: 2014-05-08
Species: All species
Last Modified: 2014-05-08
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.