Convergence of IRBIT, phosphatidylinositol (4,5) bisphosphate, and WNK/SPAK kinases in regulation of the Na+-HCO3- cotransporters family
DC Field | Value | Language |
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dc.contributor.author | Hong, Jeong Hee | - |
dc.contributor.author | Yang, Dongki | - |
dc.contributor.author | Shcheynikov, Nikolay | - |
dc.contributor.author | Ohana, Ehud | - |
dc.contributor.author | Shin, Dong Min | - |
dc.contributor.author | Muallem, Shmuel | - |
dc.date.available | 2020-02-29T00:42:40Z | - |
dc.date.created | 2020-02-06 | - |
dc.date.issued | 2013-03 | - |
dc.identifier.issn | 0027-8424 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/14674 | - |
dc.description.abstract | Fluid and HCO3- secretion is a vital function of secretory epithelia, involving basolateral HCO3- entry through the Na+-HCO3- cotransporter (NBC) NBCe1-B, and luminal HCO3- exit mediated by cystic fibrosis transmembrane conductance regulator (CFTR) and solute carrier family 26 (SLC26) Cl-/HCO3- exchangers. HCO3- secretion is highly regulated, with the WNK/SPAK kinase pathway setting the resting state and the IRBIT/PP1 pathway setting the stimulated state. However, we know little about the relationships between the WNK/SPAK and IRBIT/PP1 sites in the regulation of the transporters. The first 85 N-terminal amino acids of NBCe1-B function as an auto-inhibitory domain. Here we have identified a positively charged module within NBCe1-B(37-65) that is conserved in NBCn1-A and all 20 members of the NBC superfamily except NBCe1-A. This module is required for the interaction and activation of NBCe1-B and NBCn1-A by IRBIT and their regulation by phosphatidylinositol 4,5-bisphosphate (PIP2). Activation of the transporters by IRBIT and PIP2 is nonadditive but complementary. Phosphorylation of Ser65 mediates regulation of NBCe1-B by SPAK, and phosphorylation of Thr49 is required for regulation by IRBIT and SPAK. Sequence searches using the NBCe1-B regulatory module as a template identified a homologous sequence in the CFTR R domain and Slc26a6 sulfat transporter and antisigma factor antagonist (STAS) domain. Accordingly, the R and STAS domains bind IRBIT, and the R domain is required for activation of CFTR by IRBIT. These findings reveal convergence of regulatory modalities in a conserved domain of the NBC that may be present in other HCO3- transporters and thus in the regulation of epithelial fluid and HCO3- secretion. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | NATL ACAD SCIENCES | - |
dc.relation.isPartOf | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | - |
dc.title | Convergence of IRBIT, phosphatidylinositol (4,5) bisphosphate, and WNK/SPAK kinases in regulation of the Na+-HCO3- cotransporters family | - |
dc.type | Article | - |
dc.type.rims | ART | - |
dc.description.journalClass | 1 | - |
dc.identifier.wosid | 000316377400088 | - |
dc.identifier.doi | 10.1073/pnas.1221410110 | - |
dc.identifier.bibliographicCitation | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v.110, no.10, pp.4105 - 4110 | - |
dc.identifier.scopusid | 2-s2.0-84874589117 | - |
dc.citation.endPage | 4110 | - |
dc.citation.startPage | 4105 | - |
dc.citation.title | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | - |
dc.citation.volume | 110 | - |
dc.citation.number | 10 | - |
dc.contributor.affiliatedAuthor | Yang, Dongki | - |
dc.type.docType | Article | - |
dc.subject.keywordPlus | RECEPTOR-BINDING PROTEIN | - |
dc.subject.keywordPlus | HCO3-SALVAGE | - |
dc.subject.keywordPlus | PREDICTION | - |
dc.subject.keywordPlus | TRANSPORTERS | - |
dc.subject.keywordPlus | CLONING | - |
dc.subject.keywordPlus | AMINO | - |
dc.subject.keywordPlus | IP3 | - |
dc.relation.journalResearchArea | Science & Technology - Other Topics | - |
dc.relation.journalWebOfScienceCategory | Multidisciplinary Sciences | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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