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Article: Cloning and characterization of PDK4 on 7q21.3 encoding a fourth pyruvate dehydrogenase kinase isoenzyme in human

TitleCloning and characterization of PDK4 on 7q21.3 encoding a fourth pyruvate dehydrogenase kinase isoenzyme in human
Authors
Issue Date1996
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, 1996, v. 271 n. 37, p. 22376-22382 How to Cite?
AbstractDifferent isoenzymes of pyruvate dehydrogenase kinase (PDK) inhibit the mitochondrial pyruvate dehydrogenase complex by phosphorylation of the E1α subunit, thus contributing to the regulation of glucose metabolism. By positional cloning in the 7q21.3-q22.1 region linked with insulin resistance and non-insulin-dependent diabetes mellitus in the Pima Indians, we identified a gene encoding an additional human PDK isoform, as evidenced by its amino acid sequence identity (>65%) with other mammalian PDKs, and confirmed by biochemical analyses of the recombinant protein. We performed detailed comparative analyses of the gene, termed PDK4, in insulin-resistant and insulin-sensitive Pima Indians, and detected five DNA variants with comparable frequencies in both subject groups. Using quantitative reverse transcription polymerase chain reaction, we found that the variants identified in the promoter and 5'-untranslated region did not correlate with differences in mRNA level in skeletal muscle and adipose tissue. We conclude that alterations in PDK4 are unlikely to be the molecular basis underlying the observed linkage at 7q21.3-q22.1 in the Pima Indians. Information about the genomic organization and promoter sequences of PDK4 will be useful in studies of other members of this family of mitochondrial protein kinases that are important for the regulation of glucose metabolism.
Persistent Identifierhttp://hdl.handle.net/10722/44303
ISSN
2015 Impact Factor: 4.258
2015 SCImago Journal Rankings: 3.151
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorRowles, Jen_HK
dc.contributor.authorScherer, SWen_HK
dc.contributor.authorXi, Ten_HK
dc.contributor.authorMajer, Men_HK
dc.contributor.authorNickle, DCen_HK
dc.contributor.authorRommens, JMen_HK
dc.contributor.authorPopov, KMen_HK
dc.contributor.authorHarris, RAen_HK
dc.contributor.authorRiebow, NLen_HK
dc.contributor.authorXia, Jen_HK
dc.contributor.authorTsui, LCen_HK
dc.contributor.authorBogardus, Cen_HK
dc.contributor.authorProchazka, Men_HK
dc.date.accessioned2007-09-12T03:51:01Z-
dc.date.available2007-09-12T03:51:01Z-
dc.date.issued1996en_HK
dc.identifier.citationJournal Of Biological Chemistry, 1996, v. 271 n. 37, p. 22376-22382en_HK
dc.identifier.issn0021-9258en_HK
dc.identifier.urihttp://hdl.handle.net/10722/44303-
dc.description.abstractDifferent isoenzymes of pyruvate dehydrogenase kinase (PDK) inhibit the mitochondrial pyruvate dehydrogenase complex by phosphorylation of the E1α subunit, thus contributing to the regulation of glucose metabolism. By positional cloning in the 7q21.3-q22.1 region linked with insulin resistance and non-insulin-dependent diabetes mellitus in the Pima Indians, we identified a gene encoding an additional human PDK isoform, as evidenced by its amino acid sequence identity (>65%) with other mammalian PDKs, and confirmed by biochemical analyses of the recombinant protein. We performed detailed comparative analyses of the gene, termed PDK4, in insulin-resistant and insulin-sensitive Pima Indians, and detected five DNA variants with comparable frequencies in both subject groups. Using quantitative reverse transcription polymerase chain reaction, we found that the variants identified in the promoter and 5'-untranslated region did not correlate with differences in mRNA level in skeletal muscle and adipose tissue. We conclude that alterations in PDK4 are unlikely to be the molecular basis underlying the observed linkage at 7q21.3-q22.1 in the Pima Indians. Information about the genomic organization and promoter sequences of PDK4 will be useful in studies of other members of this family of mitochondrial protein kinases that are important for the regulation of glucose metabolism.en_HK
dc.languageengen_HK
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.rightsJournal of Biological Chemistry. Copyright © American Society for Biochemistry and Molecular Biology, Inc.en_HK
dc.subject.meshChromosomes, human, pair 7en_HK
dc.subject.meshAdipose tissue - chemistryen_HK
dc.subject.meshDna, complementary - chemistryen_HK
dc.subject.meshDiabetes mellitus, type 2 - enzymology - geneticsen_HK
dc.subject.meshIsoenzymes - geneticsen_HK
dc.titleCloning and characterization of PDK4 on 7q21.3 encoding a fourth pyruvate dehydrogenase kinase isoenzyme in humanen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0021-9258&volume=271&issue=37&spage=22376&epage=22382&date=1996&atitle=Cloning+and+characterization+of+PDK4+on+7q21.3+encoding+a+fourth+pyruvate+dehydrogenase+kinase+isoenzyme+in+humanen_HK
dc.identifier.emailTsui, LC: tsuilc@hkucc.hku.hken_HK
dc.identifier.authorityTsui, LC=rp00058en_HK
dc.description.naturelink_to_OA_fulltexten_HK
dc.identifier.doi10.1074/jbc.271.37.22376en_HK
dc.identifier.pmid8798399en_HK
dc.identifier.scopuseid_2-s2.0-9544245935en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-9544245935&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume271en_HK
dc.identifier.issue37en_HK
dc.identifier.spage22376en_HK
dc.identifier.epage22382en_HK
dc.identifier.isiWOS:A1996VG67200018-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridRowles, J=7003832492en_HK
dc.identifier.scopusauthoridScherer, SW=35374654500en_HK
dc.identifier.scopusauthoridXi, T=36889083500en_HK
dc.identifier.scopusauthoridMajer, M=36819915400en_HK
dc.identifier.scopusauthoridNickle, DC=6603553175en_HK
dc.identifier.scopusauthoridRommens, JM=7006884140en_HK
dc.identifier.scopusauthoridPopov, KM=16073194200en_HK
dc.identifier.scopusauthoridHarris, RA=35428120000en_HK
dc.identifier.scopusauthoridRiebow, NL=6505666982en_HK
dc.identifier.scopusauthoridXia, J=36930606800en_HK
dc.identifier.scopusauthoridTsui, LC=7102754167en_HK
dc.identifier.scopusauthoridBogardus, C=7102903658en_HK
dc.identifier.scopusauthoridProchazka, M=7102572739en_HK

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