DC Field | Value | Language |
---|---|---|
dc.contributor.author | Lee, Ji Hyun | ko |
dc.contributor.author | Richter, Wito | ko |
dc.contributor.author | Namkung, Wan | ko |
dc.contributor.author | Kim, Kyung Hwan | ko |
dc.contributor.author | Kim, Eunjoon | ko |
dc.contributor.author | Conti, Marco | ko |
dc.contributor.author | Lee, Min Goo | ko |
dc.date.accessioned | 2010-03-10T08:56:48Z | - |
dc.date.available | 2010-03-10T08:56:48Z | - |
dc.date.created | 2012-02-06 | - |
dc.date.created | 2012-02-06 | - |
dc.date.issued | 2007-04 | - |
dc.identifier.citation | JOURNAL OF BIOLOGICAL CHEMISTRY, v.282, no.14, pp.10414 - 10422 | - |
dc.identifier.issn | 0021-9258 | - |
dc.identifier.uri | http://hdl.handle.net/10203/17082 | - |
dc.description.abstract | Disorganized ion transport caused by hypo- or hyperfunctioning of the cystic fibrosis transmembrane conductance regulator ( CFTR) can be detrimental and may result in life-threatening diseases such as cystic fibrosis or secretory diarrhea. Thus, CFTR is controlled by elaborate positive and negative regulations for an efficient homeostasis. It has been shown that expression and activity of CFTR can be regulated either positively or negatively by PDZ ( PSD-95/ discs large/ ZO-1) domain-based adaptors. Although a positive regulation by PDZ domain-based adaptors such as EBP50/NHERF1 is established, the mechanisms for negative regulation of the CFTR by Shank2, as well as the effects of multiple adaptor interactions, are not known. Here we demonstrate a physical and physiological competition between EBP50-CFTR and Shank2-CFTR associations and the dynamic regulation of CFTR activity by these positive and negative interactions using the surface plasmon resonance assays and consecutive patch clamp experiments. Furthermore whereas EBP50 recruits a cAMP-dependent protein kinase ( PKA) complex to CFTR, Shank2 was found to be physically and functionally associated with the cyclic nucleotide phosphodiesterase PDE4D that precludes cAMP/PKA signals in epithelial cells and mouse brains. These findings strongly suggest that balanced interactions between the membrane transporter and multiple PDZ-based adaptors play a critical role in the homeostatic regulation of epithelial transport and possibly the membrane transport in other tissues. | - |
dc.description.sponsorship | This work was supported by Grant R02-2004-000-10091-0 from the Korea Research Foundation, Ministry of Education and Human Resources Development, Korea and Grant 03-PJ10-PG13-GD01-0002 from the Korea Health 21 R&D Project, Ministry of Health and Welfare, Korea (to M. G. L.) and National Institutes of Health Grant HD20788 (to M. C.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. | en |
dc.language | English | - |
dc.language.iso | en_US | en |
dc.publisher | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC | - |
dc.subject | PROTEIN-KINASE-A | - |
dc.subject | SHANK FAMILY | - |
dc.subject | DIFFERENTIAL EXPRESSION | - |
dc.subject | POSTSYNAPTIC DENSITY | - |
dc.subject | EPITHELIAL-CELLS | - |
dc.subject | EMERGING ROLE | - |
dc.subject | CAMP | - |
dc.subject | CFTR | - |
dc.subject | PHOSPHODIESTERASES | - |
dc.subject | MEMBRANE | - |
dc.title | Dynamic regulation of cystic fibrosis transmembrane conductance regulator by competitive interactions of molecular adaptors | - |
dc.type | Article | - |
dc.identifier.wosid | 000245941000032 | - |
dc.identifier.scopusid | 2-s2.0-34249859626 | - |
dc.type.rims | ART | - |
dc.citation.volume | 282 | - |
dc.citation.issue | 14 | - |
dc.citation.beginningpage | 10414 | - |
dc.citation.endingpage | 10422 | - |
dc.citation.publicationname | JOURNAL OF BIOLOGICAL CHEMISTRY | - |
dc.identifier.doi | 10.1074/jbc.M610857200 | - |
dc.embargo.liftdate | 9999-12-31 | - |
dc.embargo.terms | 9999-12-31 | - |
dc.contributor.localauthor | Kim, Eunjoon | - |
dc.contributor.nonIdAuthor | Lee, Ji Hyun | - |
dc.contributor.nonIdAuthor | Richter, Wito | - |
dc.contributor.nonIdAuthor | Namkung, Wan | - |
dc.contributor.nonIdAuthor | Kim, Kyung Hwan | - |
dc.contributor.nonIdAuthor | Conti, Marco | - |
dc.contributor.nonIdAuthor | Lee, Min Goo | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordPlus | PROTEIN-KINASE-A | - |
dc.subject.keywordPlus | SHANK FAMILY | - |
dc.subject.keywordPlus | DIFFERENTIAL EXPRESSION | - |
dc.subject.keywordPlus | POSTSYNAPTIC DENSITY | - |
dc.subject.keywordPlus | EPITHELIAL-CELLS | - |
dc.subject.keywordPlus | EMERGING ROLE | - |
dc.subject.keywordPlus | CAMP | - |
dc.subject.keywordPlus | CFTR | - |
dc.subject.keywordPlus | PHOSPHODIESTERASES | - |
dc.subject.keywordPlus | MEMBRANE | - |
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