Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/9489
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dc.contributor.authorMcRobert, E Anneen
dc.contributor.authorGallicchio, Marisaen
dc.contributor.authorJerums, Georgeen
dc.contributor.authorCooper, Mark Een
dc.contributor.authorBach, Leon Aen
dc.date.accessioned2015-05-15T22:36:10Z
dc.date.available2015-05-15T22:36:10Z
dc.date.issued2003-05-06en
dc.identifier.citationThe Journal of Biological Chemistry 2003; 278(28): 25783-9en
dc.identifier.govdoc12734202en
dc.identifier.otherPUBMEDen
dc.identifier.urihttp://ahro.austin.org.au/austinjspui/handle/1/9489en
dc.description.abstractThe presence of advanced glycation end products (AGEs) formed because of hyperglycemia in diabetic patients has been strongly linked to the development of diabetic complications and disturbances in cellular function. In this report, we describe the isolation and identification of novel AGE-binding proteins from diabetic rat kidneys. The proteins were purified by cation exchange and AGE-modified bovine serum albumin (AGE-BSA) affinity chromatography. NH2-terminal and internal sequencing identified the proteins as the NH2-terminal domains of ezrin, radixin, and moesin (ERM proteins). Using BIAcore biosensor analysis, human N-ezrin-(1-324) bound to immobilized AGE-BSA with a KD of 5.3 +/- 2.1 x 10 -7 m, whereas full-length ezrin-(1-586) and C-ezrin-(323-586) did not bind. Other glycated proteins such as AGE-RNase, N in -carboxymethyllysine (CML)-BSA, and glycated human serum albumin isolated from hyperglycemic diabetic sera competed with the immobilized AGE-BSA for binding to N-ezrin, but non-glycated BSA and RNase did not. Thus N-ezrin binds to AGEs in a glycation- and concentration-dependent manner. Phosphorylated ezrin plays a crucial role in cell shape changes, cell attachment, and cell adhesion. The effect of AGE-BSA on ezrin function was studied in a tubulogenesis model in which LLC-PK1 cell tubule formation is dependent on phosphorylated ezrin. Addition of AGE-BSA completely inhibited the ability of the cells to produce tubules. Furthermore, in vitro tyrosine phosphorylation of N-ezrin and ezrin was also inhibited by AGE-BSA. These proteins represent a novel family of intracellular binding molecules for glycated proteins and provide a potential new target for therapeutic intervention in the prevention or treatment of diabetic complications.en
dc.language.isoenen
dc.subject.otherAnimalsen
dc.subject.otherBinding Sitesen
dc.subject.otherBiosensing Techniquesen
dc.subject.otherBlood Proteins.chemistryen
dc.subject.otherBlotting, Westernen
dc.subject.otherCattleen
dc.subject.otherChromatography, Affinityen
dc.subject.otherCloning, Molecularen
dc.subject.otherCytoskeletal Proteins.chemistryen
dc.subject.otherDetergents.pharmacologyen
dc.subject.otherDiabetes Complicationsen
dc.subject.otherDiabetes Mellitus.metabolismen
dc.subject.otherDiabetes Mellitus, Experimentalen
dc.subject.otherDose-Response Relationship, Drugen
dc.subject.otherElectrophoresis, Polyacrylamide Gelen
dc.subject.otherGlycosylation End Products, Advanced.metabolismen
dc.subject.otherHumansen
dc.subject.otherKidney.metabolismen
dc.subject.otherLigandsen
dc.subject.otherLysine.analogs & derivatives.chemistryen
dc.subject.otherMembrane Proteins.chemistryen
dc.subject.otherMicrofilament Proteins.chemistryen
dc.subject.otherPhosphoproteins.chemistryen
dc.subject.otherPhosphorylationen
dc.subject.otherProtein Bindingen
dc.subject.otherProtein Structure, Tertiaryen
dc.subject.otherRatsen
dc.subject.otherRecombinant Proteins.chemistry.metabolismen
dc.subject.otherSerum Albumin.metabolismen
dc.subject.otherTime Factorsen
dc.subject.otherTumor Cells, Cultureden
dc.subject.otherTyrosine.metabolismen
dc.titleThe amino-terminal domains of the ezrin, radixin, and moesin (ERM) proteins bind advanced glycation end products, an interaction that may play a role in the development of diabetic complications.en
dc.typeJournal Articleen
dc.identifier.journaltitleThe Journal of biological chemistryen
dc.identifier.affiliationDepartment of Medicine, University of Melbourne, Austin and Repatriation Medical Centre, Heidelberg, 3084 Victoria, Australiaen
dc.identifier.doi10.1074/jbc.M210433200en
dc.description.pages25783-9en
dc.relation.urlhttps://pubmed.ncbi.nlm.nih.gov/12734202en
dc.type.austinJournal Articleen
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.fulltextNo Fulltext-
item.cerifentitytypePublications-
item.grantfulltextnone-
item.languageiso639-1en-
item.openairetypeJournal Article-
crisitem.author.deptEndocrinology-
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