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Article: Post-translational modifications of the four conserved lysine residues within the collagenous domain of adiponectin are required for the formation of its high molecular weight oligomeric complex

TitlePost-translational modifications of the four conserved lysine residues within the collagenous domain of adiponectin are required for the formation of its high molecular weight oligomeric complex
Authors
Issue Date2006
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, 2006, v. 281 n. 24, p. 16391-16400 How to Cite?
AbstractAdiponectin is a multifunctional adipokine that circulates as several oligomeric complexes in the blood stream. However, the molecular basis that regulates the production of the adiponectin oligomers remains largely elusive. We have shown previously that several conserved lysine residues (positions 68, 71, 80, and 104) within the collagenous domain of adiponectin are modified by hydroxylation and glycosylation (Wang, Y., Xu, A., Knight, C., Xu, L. Y., and Cooper, G. J. (2002) J. Biol. Chem. 277, 19521-19529). Here, we investigated the potential roles of these post-translational modifications in oligomeric complex formation of adiponectin. Gel filtration chromatography revealed that adiponectin produced from mammalian cells formed trimeric, hexameric, and high molecular weight (HMW) oligomeric complexes. These three oligomeric forms were differentially glycosylated, with the HMW oligomer having the highest carbohydrate content. Disruption of hydroxylation and glycosylation by substitution of the four conserved lysines with arginines selectively abrogated the intracellular assembly of the HMW oligomers in vitro as well as in vivo. In type 2 diabetic patients, both the ratios of HMW to total adiponectin and the degree of adiponectin glycosylation were significantly decreased compared with healthy controls. Functional studies of adiponectin-null mice revealed that abrogation of lysine hydroxylation/glycosylation markedly decreased the ability of adiponectin to stimulate phosphorylation of AMP-activated protein kinase in liver tissue. Chronic treatment of db/db diabetic mice with wild-type adiponectin alleviated hyperglycemia, hypertriglyceridemia, hepatic steatosis, and insulin resistance, whereas full-length adiponectin without proper post-translational modifications and HMW oligomers showed substantially decreased activities. Taken together, these data suggest that hydroxylation and glycosylation of the lysine residues within the collagenous domain of adiponectin are critically involved in regulating the formation of its HMW oligomeric complex and consequently contribute to the insulin-sensitizing activity of adiponectin in hepatocytes. © 2006 by The American Society for Biochemistry and Molecular Biology, Inc.
Persistent Identifierhttp://hdl.handle.net/10722/77319
ISSN
2015 Impact Factor: 4.258
2015 SCImago Journal Rankings: 3.151
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorWang, Yen_HK
dc.contributor.authorLam, KSLen_HK
dc.contributor.authorChan, Len_HK
dc.contributor.authorKok, WCen_HK
dc.contributor.authorLam, JBBen_HK
dc.contributor.authorLam, MCen_HK
dc.contributor.authorHoo, RCLen_HK
dc.contributor.authorMak, WWNen_HK
dc.contributor.authorCooper, GJSen_HK
dc.contributor.authorXu, Aen_HK
dc.date.accessioned2010-09-06T07:30:37Z-
dc.date.available2010-09-06T07:30:37Z-
dc.date.issued2006en_HK
dc.identifier.citationJournal Of Biological Chemistry, 2006, v. 281 n. 24, p. 16391-16400en_HK
dc.identifier.issn0021-9258en_HK
dc.identifier.urihttp://hdl.handle.net/10722/77319-
dc.description.abstractAdiponectin is a multifunctional adipokine that circulates as several oligomeric complexes in the blood stream. However, the molecular basis that regulates the production of the adiponectin oligomers remains largely elusive. We have shown previously that several conserved lysine residues (positions 68, 71, 80, and 104) within the collagenous domain of adiponectin are modified by hydroxylation and glycosylation (Wang, Y., Xu, A., Knight, C., Xu, L. Y., and Cooper, G. J. (2002) J. Biol. Chem. 277, 19521-19529). Here, we investigated the potential roles of these post-translational modifications in oligomeric complex formation of adiponectin. Gel filtration chromatography revealed that adiponectin produced from mammalian cells formed trimeric, hexameric, and high molecular weight (HMW) oligomeric complexes. These three oligomeric forms were differentially glycosylated, with the HMW oligomer having the highest carbohydrate content. Disruption of hydroxylation and glycosylation by substitution of the four conserved lysines with arginines selectively abrogated the intracellular assembly of the HMW oligomers in vitro as well as in vivo. In type 2 diabetic patients, both the ratios of HMW to total adiponectin and the degree of adiponectin glycosylation were significantly decreased compared with healthy controls. Functional studies of adiponectin-null mice revealed that abrogation of lysine hydroxylation/glycosylation markedly decreased the ability of adiponectin to stimulate phosphorylation of AMP-activated protein kinase in liver tissue. Chronic treatment of db/db diabetic mice with wild-type adiponectin alleviated hyperglycemia, hypertriglyceridemia, hepatic steatosis, and insulin resistance, whereas full-length adiponectin without proper post-translational modifications and HMW oligomers showed substantially decreased activities. Taken together, these data suggest that hydroxylation and glycosylation of the lysine residues within the collagenous domain of adiponectin are critically involved in regulating the formation of its HMW oligomeric complex and consequently contribute to the insulin-sensitizing activity of adiponectin in hepatocytes. © 2006 by The American Society for Biochemistry and Molecular Biology, Inc.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.meshAdipocytes - metabolismen_HK
dc.subject.meshAdiponectin - chemistryen_HK
dc.subject.meshAnimalsen_HK
dc.subject.meshGlycosylationen_HK
dc.subject.meshHepatocytes - metabolismen_HK
dc.subject.meshHumansen_HK
dc.subject.meshLysine - chemistryen_HK
dc.subject.meshMaleen_HK
dc.subject.meshMiceen_HK
dc.subject.meshMice, Inbred C57BLen_HK
dc.subject.meshMutagenesis, Site-Directeden_HK
dc.subject.meshProtein Processing, Post-Translationalen_HK
dc.subject.meshProtein Structure, Tertiaryen_HK
dc.subject.meshRatsen_HK
dc.titlePost-translational modifications of the four conserved lysine residues within the collagenous domain of adiponectin are required for the formation of its high molecular weight oligomeric complexen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0021-9258&volume=281&spage=16391&epage=400&date=2006&atitle=Post-translational+modifications+of+the+four+conserved+lysine+residues+within+the+collagenous+domain+of+adiponectin+are+required+for+the+formation+of+its+high+molecular+weight+oligomeric+complexen_HK
dc.identifier.emailWang, Y: yuwanghk@hku.hken_HK
dc.identifier.emailLam, KSL: ksllam@hku.hken_HK
dc.identifier.emailHoo, RCL: rubyhoo@hkucc.hku.hken_HK
dc.identifier.emailXu, A: amxu@hkucc.hku.hken_HK
dc.identifier.authorityWang, Y=rp00239en_HK
dc.identifier.authorityLam, KSL=rp00343en_HK
dc.identifier.authorityHoo, RCL=rp01334en_HK
dc.identifier.authorityXu, A=rp00485en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1074/jbc.M513907200en_HK
dc.identifier.pmid16621799-
dc.identifier.scopuseid_2-s2.0-33745222085en_HK
dc.identifier.hkuros126093en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-33745222085&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume281en_HK
dc.identifier.issue24en_HK
dc.identifier.spage16391en_HK
dc.identifier.epage16400en_HK
dc.identifier.isiWOS:000238165700028-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridWang, Y=34973733700en_HK
dc.identifier.scopusauthoridLam, KSL=8082870600en_HK
dc.identifier.scopusauthoridChan, L=24439401800en_HK
dc.identifier.scopusauthoridKok, WC=14018106400en_HK
dc.identifier.scopusauthoridLam, JBB=24448474900en_HK
dc.identifier.scopusauthoridLam, MC=36879143100en_HK
dc.identifier.scopusauthoridHoo, RCL=6602369766en_HK
dc.identifier.scopusauthoridMak, WWN=7005317285en_HK
dc.identifier.scopusauthoridCooper, GJS=7402355946en_HK
dc.identifier.scopusauthoridXu, A=7202655409en_HK

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