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Article: Protein kinase CK2, cystic fibrosis transmembrane conductance regulator, and the ΔF508 mutation: F508 deletion disrupts a kinase-binding site

TitleProtein kinase CK2, cystic fibrosis transmembrane conductance regulator, and the ΔF508 mutation: F508 deletion disrupts a kinase-binding site
Authors
Issue Date2007
PublisherAmerican 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?
AbstractDeletion 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 Identifierhttp://hdl.handle.net/10722/137016
ISSN
2015 Impact Factor: 4.258
2015 SCImago Journal Rankings: 3.151
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorTreharne, KJen_HK
dc.contributor.authorCrawford, RMen_HK
dc.contributor.authorXu, Zen_HK
dc.contributor.authorChen, JHen_HK
dc.contributor.authorBest, OGen_HK
dc.contributor.authorSchulte, EAen_HK
dc.contributor.authorGruenert, DCen_HK
dc.contributor.authorWilson, SMen_HK
dc.contributor.authorSheppard, DNen_HK
dc.contributor.authorKunzelmann, Ken_HK
dc.contributor.authorMehta, Aen_HK
dc.date.accessioned2011-07-29T02:14:20Z-
dc.date.available2011-07-29T02:14:20Z-
dc.date.issued2007en_HK
dc.identifier.citationJournal Of Biological Chemistry, 2007, v. 282 n. 14, p. 10804-10813en_HK
dc.identifier.issn0021-9258en_HK
dc.identifier.urihttp://hdl.handle.net/10722/137016-
dc.description.abstractDeletion 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.languageengen_US
dc.publisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/en_HK
dc.relation.ispartofJournal of Biological Chemistryen_HK
dc.titleProtein kinase CK2, cystic fibrosis transmembrane conductance regulator, and the ΔF508 mutation: F508 deletion disrupts a kinase-binding siteen_HK
dc.typeArticleen_HK
dc.identifier.emailChen, JH: jhlchen@hku.hken_HK
dc.identifier.authorityChen, JH=rp01518en_HK
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1074/jbc.M610956200en_HK
dc.identifier.pmid17289674en_HK
dc.identifier.scopuseid_2-s2.0-34249845170en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-34249845170&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume282en_HK
dc.identifier.issue14en_HK
dc.identifier.spage10804en_HK
dc.identifier.epage10813en_HK
dc.identifier.eissn1083-351X-
dc.identifier.isiWOS:000245941000074-
dc.publisher.placeUnited Statesen_HK
dc.identifier.f10001086846-
dc.identifier.scopusauthoridTreharne, KJ=6602620652en_HK
dc.identifier.scopusauthoridCrawford, RM=36753119100en_HK
dc.identifier.scopusauthoridXu, Z=14055096400en_HK
dc.identifier.scopusauthoridChen, JH=7501878156en_HK
dc.identifier.scopusauthoridBest, OG=6505763839en_HK
dc.identifier.scopusauthoridSchulte, EA=16424316200en_HK
dc.identifier.scopusauthoridGruenert, DC=7005195617en_HK
dc.identifier.scopusauthoridWilson, SM=35546851700en_HK
dc.identifier.scopusauthoridSheppard, DN=7201812458en_HK
dc.identifier.scopusauthoridKunzelmann, K=7005750781en_HK
dc.identifier.scopusauthoridMehta, A=7402756457en_HK

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