Cited 61 times in
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 | 신동민 | - |
dc.date.accessioned | 2014-12-18T08:36:46Z | - |
dc.date.available | 2014-12-18T08:36:46Z | - |
dc.date.issued | 2013 | - |
dc.identifier.issn | 0027-8424 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/86631 | - |
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 autoinhibitory 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.description.statementOfResponsibility | open | - |
dc.relation.isPartOf | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.subject.MESH | Amino Acid Sequence | - |
dc.subject.MESH | Binding Sites | - |
dc.subject.MESH | Cystic Fibrosis Transmembrane Conductance Regulator/chemistry | - |
dc.subject.MESH | Cystic Fibrosis Transmembrane Conductance Regulator/genetics | - |
dc.subject.MESH | Cystic Fibrosis Transmembrane Conductance Regulator/metabolism | - |
dc.subject.MESH | HeLa Cells | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Lectins, C-Type/metabolism* | - |
dc.subject.MESH | Membrane Proteins/metabolism* | - |
dc.subject.MESH | Models, Molecular | - |
dc.subject.MESH | Molecular Sequence Data | - |
dc.subject.MESH | Phosphatidylinositol 4,5-Diphosphate/metabolism* | - |
dc.subject.MESH | Phosphorylation | - |
dc.subject.MESH | Protein-Serine-Threonine Kinases/metabolism* | - |
dc.subject.MESH | Recombinant Proteins/chemistry | - |
dc.subject.MESH | Recombinant Proteins/genetics | - |
dc.subject.MESH | Recombinant Proteins/metabolism | - |
dc.subject.MESH | Sequence Homology, Amino Acid | - |
dc.subject.MESH | Signal Transduction | - |
dc.subject.MESH | Sodium-Bicarbonate Symporters/chemistry | - |
dc.subject.MESH | Sodium-Bicarbonate Symporters/genetics | - |
dc.subject.MESH | Sodium-Bicarbonate Symporters/metabolism* | - |
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.contributor.college | College of Dentistry (치과대학) | - |
dc.contributor.department | Dept. of Oral Biology (구강생물학) | - |
dc.contributor.googleauthor | Jeong Hee Hong | - |
dc.contributor.googleauthor | Dongki Yang | - |
dc.contributor.googleauthor | Nikolay Shcheynikov | - |
dc.contributor.googleauthor | Ehud Ohana | - |
dc.contributor.googleauthor | Dong Min Shin | - |
dc.contributor.googleauthor | Shmuel Muallem | - |
dc.identifier.doi | 10.1073/pnas.1221410110 | - |
dc.admin.author | false | - |
dc.admin.mapping | false | - |
dc.contributor.localId | A02091 | - |
dc.relation.journalcode | J02550 | - |
dc.identifier.eissn | 1091-6490 | - |
dc.identifier.pmid | 23431199 | - |
dc.subject.keyword | Amino Acid Sequence | - |
dc.subject.keyword | Binding Sites | - |
dc.subject.keyword | Cystic Fibrosis Transmembrane Conductance Regulator/chemistry | - |
dc.subject.keyword | Cystic Fibrosis Transmembrane Conductance Regulator/genetics | - |
dc.subject.keyword | Cystic Fibrosis Transmembrane Conductance Regulator/metabolism | - |
dc.subject.keyword | HeLa Cells | - |
dc.subject.keyword | Humans | - |
dc.subject.keyword | Lectins, C-Type/metabolism* | - |
dc.subject.keyword | Membrane Proteins/metabolism* | - |
dc.subject.keyword | Models, Molecular | - |
dc.subject.keyword | Molecular Sequence Data | - |
dc.subject.keyword | Phosphatidylinositol 4,5-Diphosphate/metabolism* | - |
dc.subject.keyword | Phosphorylation | - |
dc.subject.keyword | Protein-Serine-Threonine Kinases/metabolism* | - |
dc.subject.keyword | Recombinant Proteins/chemistry | - |
dc.subject.keyword | Recombinant Proteins/genetics | - |
dc.subject.keyword | Recombinant Proteins/metabolism | - |
dc.subject.keyword | Sequence Homology, Amino Acid | - |
dc.subject.keyword | Signal Transduction | - |
dc.subject.keyword | Sodium-Bicarbonate Symporters/chemistry | - |
dc.subject.keyword | Sodium-Bicarbonate Symporters/genetics | - |
dc.subject.keyword | Sodium-Bicarbonate Symporters/metabolism* | - |
dc.contributor.alternativeName | Shin, Dong Min | - |
dc.contributor.affiliatedAuthor | Shin, Dong Min | - |
dc.rights.accessRights | free | - |
dc.citation.volume | 110 | - |
dc.citation.number | 10 | - |
dc.citation.startPage | 4105 | - |
dc.citation.endPage | 4110 | - |
dc.identifier.bibliographicCitation | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol.110(10) : 4105-4110, 2013 | - |
dc.identifier.rimsid | 29105 | - |
dc.type.rims | ART | - |
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