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Article: The roles of the PDZ-containing proteins bridge-1 and PDZD2 in the regulation of insulin production and pancreatic beta-cell mass

TitleThe roles of the PDZ-containing proteins bridge-1 and PDZD2 in the regulation of insulin production and pancreatic beta-cell mass
Authors
KeywordsBridge-1
Insulin
Pancreas
PDZ
PDZD2
Issue Date2009
PublisherBentham Science Publishers Ltd. The Journal's web site is located at http://www.bentham.org/cpps/index.htm
Citation
Current Protein And Peptide Science, 2009, v. 10 n. 1, p. 30-36 How to Cite?
AbstractPDZ domains are versatile protein interaction modules with the ability to dimerize and to recognize internal and carboxy-terminal peptide motifs. Their function in mediating the formation of multi-molecular signaling complexes is best understood at neuronal and epithelial membranes. In a screen for interactors that regulate transcription factor function in pancreatic beta cells, we isolated two PDZ-containing proteins Bridge-1 (PSMD9) and PDZD2, which contain one and six PDZ domains, respectively. Here, we review their functions in the regulation of pancreatic beta cells as a nuclear coactivator or extracellular signaling molecule. Bridge-1 interacts with both E12 and PDX-1 to stimulate insulin promoter activity. Recent gain-of-function analysis in both cell and transgenic models has revealed its functions to regulate both insulin gene expression and pancreatic beta-cell survival. Little is known about the intracellular function of PDZD2 that is predominantly localized to the endoplasmic reticulum of INS-1E cells. Interestingly, PDZD2 is proteolytically processed by caspase-3 to generate a carboxy-terminal secreted protein (sPDZD2) containing two PDZ domains. Expressed in fetal pancreatic progenitor and INS-1E cells, sPDZD2 when added as recombinant protein exerts concentration-dependent mitogenic effects on beta-like cells. We propose that the PDZ domain proteins Bridge-1 and PDZD2 likely transduce signals that regulate insulin production, proliferation, and survival of pancreatic beta cells. © 2009 Bentham Science Publishers Ltd.
Persistent Identifierhttp://hdl.handle.net/10722/58276
ISSN
2023 Impact Factor: 1.9
2023 SCImago Journal Rankings: 0.527
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorThomas, MKen_HK
dc.contributor.authorTsang, SWen_HK
dc.contributor.authorYeung, MLen_HK
dc.contributor.authorLeung, PSen_HK
dc.contributor.authorYao, KMen_HK
dc.date.accessioned2010-05-31T03:27:16Z-
dc.date.available2010-05-31T03:27:16Z-
dc.date.issued2009en_HK
dc.identifier.citationCurrent Protein And Peptide Science, 2009, v. 10 n. 1, p. 30-36en_HK
dc.identifier.issn1389-2037en_HK
dc.identifier.urihttp://hdl.handle.net/10722/58276-
dc.description.abstractPDZ domains are versatile protein interaction modules with the ability to dimerize and to recognize internal and carboxy-terminal peptide motifs. Their function in mediating the formation of multi-molecular signaling complexes is best understood at neuronal and epithelial membranes. In a screen for interactors that regulate transcription factor function in pancreatic beta cells, we isolated two PDZ-containing proteins Bridge-1 (PSMD9) and PDZD2, which contain one and six PDZ domains, respectively. Here, we review their functions in the regulation of pancreatic beta cells as a nuclear coactivator or extracellular signaling molecule. Bridge-1 interacts with both E12 and PDX-1 to stimulate insulin promoter activity. Recent gain-of-function analysis in both cell and transgenic models has revealed its functions to regulate both insulin gene expression and pancreatic beta-cell survival. Little is known about the intracellular function of PDZD2 that is predominantly localized to the endoplasmic reticulum of INS-1E cells. Interestingly, PDZD2 is proteolytically processed by caspase-3 to generate a carboxy-terminal secreted protein (sPDZD2) containing two PDZ domains. Expressed in fetal pancreatic progenitor and INS-1E cells, sPDZD2 when added as recombinant protein exerts concentration-dependent mitogenic effects on beta-like cells. We propose that the PDZ domain proteins Bridge-1 and PDZD2 likely transduce signals that regulate insulin production, proliferation, and survival of pancreatic beta cells. © 2009 Bentham Science Publishers Ltd.en_HK
dc.languageengen_HK
dc.publisherBentham Science Publishers Ltd. The Journal's web site is located at http://www.bentham.org/cpps/index.htmen_HK
dc.relation.ispartofCurrent Protein and Peptide Scienceen_HK
dc.subjectBridge-1en_HK
dc.subjectInsulinen_HK
dc.subjectPancreasen_HK
dc.subjectPDZen_HK
dc.subjectPDZD2en_HK
dc.subject.meshAdaptor Proteins, Signal Transducing - isolation & purification - metabolismen_HK
dc.subject.meshAnimalsen_HK
dc.subject.meshHumansen_HK
dc.subject.meshInsulin - metabolismen_HK
dc.subject.meshInsulin-Secreting Cells - chemistry - cytology - metabolismen_HK
dc.subject.meshNeoplasm Proteins - isolation & purification - metabolismen_HK
dc.subject.meshProteasome Endopeptidase Complex - genetics - isolation & purification - metabolismen_HK
dc.subject.meshTrans-Activators - genetics - isolation & purification - metabolismen_HK
dc.titleThe roles of the PDZ-containing proteins bridge-1 and PDZD2 in the regulation of insulin production and pancreatic beta-cell massen_HK
dc.typeArticleen_HK
dc.identifier.emailYeung, ML:pmlyeung@hku.hken_HK
dc.identifier.emailYao, KM:kmyao@hku.hken_HK
dc.identifier.authorityYeung, ML=rp01402en_HK
dc.identifier.authorityYao, KM=rp00344en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.2174/138920309787315248en_HK
dc.identifier.pmid19275670en_HK
dc.identifier.scopuseid_2-s2.0-63849182778en_HK
dc.identifier.hkuros157209en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-63849182778&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume10en_HK
dc.identifier.issue1en_HK
dc.identifier.spage30en_HK
dc.identifier.epage36en_HK
dc.identifier.isiWOS:000263968500005-
dc.publisher.placeNetherlandsen_HK
dc.identifier.scopusauthoridThomas, MK=7404754193en_HK
dc.identifier.scopusauthoridTsang, SW=8050597200en_HK
dc.identifier.scopusauthoridYeung, ML=8350940900en_HK
dc.identifier.scopusauthoridLeung, PS=7401748938en_HK
dc.identifier.scopusauthoridYao, KM=7403234578en_HK
dc.identifier.citeulike3987698-
dc.identifier.issnl1389-2037-

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