DC Field | Value | Language |
---|---|---|
dc.contributor.author | Lee, Jung-Soo | ko |
dc.contributor.author | Lee, Young Mee | ko |
dc.contributor.author | Kim, Joo Young | ko |
dc.contributor.author | Park, Hyun Woo | ko |
dc.contributor.author | Grinstein, Sergio | ko |
dc.contributor.author | Orlowski, John | ko |
dc.contributor.author | Kim, Eunjoon | ko |
dc.contributor.author | Kim, Kyung Hwan | ko |
dc.contributor.author | Lee, Min Goo | ko |
dc.date.accessioned | 2013-03-09T22:07:15Z | - |
dc.date.available | 2013-03-09T22:07:15Z | - |
dc.date.created | 2012-02-06 | - |
dc.date.created | 2012-02-06 | - |
dc.date.issued | 2010-03 | - |
dc.identifier.citation | JOURNAL OF BIOLOGICAL CHEMISTRY, v.285, no.11, pp.8104 - 8113 | - |
dc.identifier.issn | 0021-9258 | - |
dc.identifier.uri | http://hdl.handle.net/10203/97599 | - |
dc.description.abstract | Na+/H+ exchanger 3 (NHE3) plays an important role in neutral Na+ transport in mammalian epithelial cells. The Rho family of small GTPases and the PDZ (PSD-95/discs large/ZO-1) domain-based adaptor Shank2 are known to regulate the membrane expression and activity of NHE3. In this study we examined the role of beta Pix, a guanine nucleotide exchange factor for the Rho GTPase and a strong binding partner to Shank2, in NHE3 regulation using integrated molecular and physiological approaches. Immunoprecipitation and pulldown assays revealed that NHE3, Shank2, and beta Pix form a macromolecular complex when expressed heterologously in mammalian cells as well as endogenously in rat colon, kidney, and pancreas. In addition, these proteins co-segregated at the apical surface of rat colonic epithelial cells, as detected by immunofluorescence staining. When expressed in PS120/NHE3 cells, beta Pix increased membrane expression and basal activity of NHE3. Interestingly, the effects of beta Pix on NHE3 were abolished by cotransfection with dominant-negative Shank2 mutants and by treatment with Clostridium difficile toxin B, a Rho GTPase inhibitor, indicating that Shank2 and Rho GTPases are involved in beta Pix-mediated NHE3 regulation. Knockdown of endogenous beta Pix by RNA interference decreased Shank2-induced increase of NHE3 membrane expression in HEK 293T cells. These results indicate that beta Pix up-regulates NHE3 membrane expression and activity by Shank2-mediated protein-protein interaction and by activating Rho GTPases in the apical regions of epithelial cells. | - |
dc.language | English | - |
dc.publisher | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC | - |
dc.subject | TRANSMEMBRANE CONDUCTANCE REGULATOR | - |
dc.subject | SHANK FAMILY | - |
dc.subject | EPITHELIAL-CELLS | - |
dc.subject | PROXIMAL TUBULE | - |
dc.subject | APICAL MEMBRANE | - |
dc.subject | PANCREATIC DUCT | - |
dc.subject | FOCAL ADHESION | - |
dc.subject | RHO-GTPASES | - |
dc.subject | KINASE-A | - |
dc.subject | NHE3 | - |
dc.title | βPix Up-regulates Na+/H+ Exchanger 3 through a Shank2-mediated Protein-Protein Interaction | - |
dc.type | Article | - |
dc.identifier.wosid | 000275413800028 | - |
dc.identifier.scopusid | 2-s2.0-77950901355 | - |
dc.type.rims | ART | - |
dc.citation.volume | 285 | - |
dc.citation.issue | 11 | - |
dc.citation.beginningpage | 8104 | - |
dc.citation.endingpage | 8113 | - |
dc.citation.publicationname | JOURNAL OF BIOLOGICAL CHEMISTRY | - |
dc.contributor.localauthor | Kim, Eunjoon | - |
dc.contributor.nonIdAuthor | Lee, Jung-Soo | - |
dc.contributor.nonIdAuthor | Lee, Young Mee | - |
dc.contributor.nonIdAuthor | Kim, Joo Young | - |
dc.contributor.nonIdAuthor | Park, Hyun Woo | - |
dc.contributor.nonIdAuthor | Grinstein, Sergio | - |
dc.contributor.nonIdAuthor | Orlowski, John | - |
dc.contributor.nonIdAuthor | Kim, Kyung Hwan | - |
dc.contributor.nonIdAuthor | Lee, Min Goo | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordPlus | TRANSMEMBRANE CONDUCTANCE REGULATOR | - |
dc.subject.keywordPlus | SHANK FAMILY | - |
dc.subject.keywordPlus | EPITHELIAL-CELLS | - |
dc.subject.keywordPlus | PROXIMAL TUBULE | - |
dc.subject.keywordPlus | APICAL MEMBRANE | - |
dc.subject.keywordPlus | PANCREATIC DUCT | - |
dc.subject.keywordPlus | FOCAL ADHESION | - |
dc.subject.keywordPlus | RHO-GTPASES | - |
dc.subject.keywordPlus | KINASE-A | - |
dc.subject.keywordPlus | NHE3 | - |
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