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- Publisher Website: 10.1074/jbc.M610956200
- Scopus: eid_2-s2.0-34249845170
- PMID: 17289674
- WOS: WOS:000245941000074
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Article: Protein kinase CK2, cystic fibrosis transmembrane conductance regulator, and the ΔF508 mutation: F508 deletion disrupts a kinase-binding site
Title | Protein kinase CK2, cystic fibrosis transmembrane conductance regulator, and the ΔF508 mutation: F508 deletion disrupts a kinase-binding site |
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Authors | |
Issue Date | 2007 |
Publisher | American Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/ |
Citation | Journal Of Biological Chemistry, 2007, v. 282 n. 14, p. 10804-10813 How to Cite? |
Abstract | Deletion of phenylalanine 508 (ΔF508) from the first nucleotide-binding domain (NBD1) of the cystic fibrosis transmembrane conductance regulator (CFTR) is the most common mutation in cystic fibrosis. The F508 region lies within a surface-exposed loop that has not been assigned any interaction with associated proteins. Here we demonstrate that the pleiotropic protein kinase CK2 that controls protein trafficking, cell proliferation, and development binds wild-type CFTR near F508 and phosphorylates NBD1 at Ser-511 in vivo and that mutation of Ser-511 disrupts CFTR channel gating. Importantly, the interaction of CK2 with NBD1 is selectively abrogated by the ΔF508 mutation without disrupting four established CFTR-associated kinases and two phosphatases. Loss of CK2 association is functionally corroborated by the insensitivity of ΔF508-CFTR to CK2 inhibition, the absence of CK2 activity in ΔF508 CFTR-expressing cell membranes, and inhibition of CFTR channel activity by a peptide that mimics the F508 region of CFTR (but not the equivalent ΔF508 peptide). Disruption of this CK2-CFTR association is the first described ΔF508-dependent protein-protein interaction that provides a new molecular paradigm in the most frequent form of cystic fibrosis. © 2007 by The American Society for Biochemistry and Molecular Biology, Inc. |
Persistent Identifier | http://hdl.handle.net/10722/137016 |
ISSN | 2020 Impact Factor: 5.157 2023 SCImago Journal Rankings: 1.766 |
ISI Accession Number ID | |
References |
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Treharne, KJ | en_HK |
dc.contributor.author | Crawford, RM | en_HK |
dc.contributor.author | Xu, Z | en_HK |
dc.contributor.author | Chen, JH | en_HK |
dc.contributor.author | Best, OG | en_HK |
dc.contributor.author | Schulte, EA | en_HK |
dc.contributor.author | Gruenert, DC | en_HK |
dc.contributor.author | Wilson, SM | en_HK |
dc.contributor.author | Sheppard, DN | en_HK |
dc.contributor.author | Kunzelmann, K | en_HK |
dc.contributor.author | Mehta, A | en_HK |
dc.date.accessioned | 2011-07-29T02:14:20Z | - |
dc.date.available | 2011-07-29T02:14:20Z | - |
dc.date.issued | 2007 | en_HK |
dc.identifier.citation | Journal Of Biological Chemistry, 2007, v. 282 n. 14, p. 10804-10813 | en_HK |
dc.identifier.issn | 0021-9258 | en_HK |
dc.identifier.uri | http://hdl.handle.net/10722/137016 | - |
dc.description.abstract | Deletion of phenylalanine 508 (ΔF508) from the first nucleotide-binding domain (NBD1) of the cystic fibrosis transmembrane conductance regulator (CFTR) is the most common mutation in cystic fibrosis. The F508 region lies within a surface-exposed loop that has not been assigned any interaction with associated proteins. Here we demonstrate that the pleiotropic protein kinase CK2 that controls protein trafficking, cell proliferation, and development binds wild-type CFTR near F508 and phosphorylates NBD1 at Ser-511 in vivo and that mutation of Ser-511 disrupts CFTR channel gating. Importantly, the interaction of CK2 with NBD1 is selectively abrogated by the ΔF508 mutation without disrupting four established CFTR-associated kinases and two phosphatases. Loss of CK2 association is functionally corroborated by the insensitivity of ΔF508-CFTR to CK2 inhibition, the absence of CK2 activity in ΔF508 CFTR-expressing cell membranes, and inhibition of CFTR channel activity by a peptide that mimics the F508 region of CFTR (but not the equivalent ΔF508 peptide). Disruption of this CK2-CFTR association is the first described ΔF508-dependent protein-protein interaction that provides a new molecular paradigm in the most frequent form of cystic fibrosis. © 2007 by The American Society for Biochemistry and Molecular Biology, Inc. | en_HK |
dc.language | eng | en_US |
dc.publisher | American Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/ | en_HK |
dc.relation.ispartof | Journal of Biological Chemistry | en_HK |
dc.title | Protein kinase CK2, cystic fibrosis transmembrane conductance regulator, and the ΔF508 mutation: F508 deletion disrupts a kinase-binding site | en_HK |
dc.type | Article | en_HK |
dc.identifier.email | Chen, JH: jhlchen@hku.hk | en_HK |
dc.identifier.authority | Chen, JH=rp01518 | en_HK |
dc.description.nature | link_to_subscribed_fulltext | en_US |
dc.identifier.doi | 10.1074/jbc.M610956200 | en_HK |
dc.identifier.pmid | 17289674 | en_HK |
dc.identifier.scopus | eid_2-s2.0-34249845170 | en_HK |
dc.relation.references | http://www.scopus.com/mlt/select.url?eid=2-s2.0-34249845170&selection=ref&src=s&origin=recordpage | en_HK |
dc.identifier.volume | 282 | en_HK |
dc.identifier.issue | 14 | en_HK |
dc.identifier.spage | 10804 | en_HK |
dc.identifier.epage | 10813 | en_HK |
dc.identifier.eissn | 1083-351X | - |
dc.identifier.isi | WOS:000245941000074 | - |
dc.publisher.place | United States | en_HK |
dc.identifier.f1000 | 1086846 | - |
dc.identifier.scopusauthorid | Treharne, KJ=6602620652 | en_HK |
dc.identifier.scopusauthorid | Crawford, RM=36753119100 | en_HK |
dc.identifier.scopusauthorid | Xu, Z=14055096400 | en_HK |
dc.identifier.scopusauthorid | Chen, JH=7501878156 | en_HK |
dc.identifier.scopusauthorid | Best, OG=6505763839 | en_HK |
dc.identifier.scopusauthorid | Schulte, EA=16424316200 | en_HK |
dc.identifier.scopusauthorid | Gruenert, DC=7005195617 | en_HK |
dc.identifier.scopusauthorid | Wilson, SM=35546851700 | en_HK |
dc.identifier.scopusauthorid | Sheppard, DN=7201812458 | en_HK |
dc.identifier.scopusauthorid | Kunzelmann, K=7005750781 | en_HK |
dc.identifier.scopusauthorid | Mehta, A=7402756457 | en_HK |
dc.identifier.issnl | 0021-9258 | - |