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Article: An isoleucine-zipper motif enhances costimulation of human soluble trimeric GITR ligand

TitleAn isoleucine-zipper motif enhances costimulation of human soluble trimeric GITR ligand
Authors
KeywordsGitr Ligand
Isoleucine Zipper
T Cells
Issue Date2010
PublisherChinese Society of Immunology. The Journal's web site is located at http://www.nature.com/cmi/index.html
Citation
Cellular And Molecular Immunology, 2010, v. 7 n. 4, p. 316-322 How to Cite?
Abstract
Glucocorticoid-induced tumor-necrosis factor receptor (GITR) and its ligand, GITRL, play significant roles in regulating immune responses. It is clear that human soluble GITRL (hsGITRL) transduces signal activity through multiple oligomerization states. To develop human soluble trimeric GITRL protein as a potential therapeutic target, we explored the link of the isoleucine-zipper (ILZ) motif to the N-terminus of the human soluble GITRL with two leucine sequences. hsGITRL, with the ILZ motif (ILZ-hsGITRL), was firstly expressed in Escherichia coli, which exhibited a predominant trimer when identified by Sephadex G-100 filtration and non-reducing SDS-polyacrylamide gel electrophoresis (SDS-PAGE). The significantly higher biological activity of the ILZ-hsGITRL compared with hsGITRL was confirmed by CD4 T proliferation, interferon-γ (IFN-γ) secretion and binding activity assay. To reveal and compare the underlying mechanisms, the level of extracellular signal-regulated kinase-1/2 (ERK1/2) phosphorylation was examined, indicating that ILZ-hsGITRL induced more persistent and stronger ERK1/2 activation than hsGITRL. In conclusion, the incorporation of an ILZ motif could markedly improve the costimulation of hsGITRL. © 2010 CSI and USTC. All rights reserved.
DescriptionNature free article
Persistent Identifierhttp://hdl.handle.net/10722/148630
ISSN
2013 Impact Factor: 4.185
ISI Accession Number ID
Funding AgencyGrant Number
National Natural Science Foundation of China30871193
30972748
Natural Science Foundation of Jiangsu ProvinceBK2004405
Natural Science Foundation of Jiangsu Province Educational Commission08KJB320002
Research Foundation of Jiangsu Province Health DepartmentH200952
Jiangsu University
SCI-Tech Innovation Team of Jiangsu University
Funding Information:

This study was supported by the National Natural Science Foundation of China (Grant No. 30871193 and No. 30972748), Natural Science Foundation of Jiangsu Province (Grant No. BK2004405), Natural Science Foundation of Jiangsu Province Educational Commission (Grant No. 08KJB320002), Research Foundation of Jiangsu Province Health Department (Grant No. H200952), and Top Talent Program of Jiangsu University and SCI-Tech Innovation Team of Jiangsu University.

References

 

Author Affiliations
  1. Jiangsu University
  2. The University of Hong Kong
  3. Zhejiang University
DC FieldValueLanguage
dc.contributor.authorCui, Den_US
dc.contributor.authorWang, Sen_US
dc.contributor.authorChen, Yen_US
dc.contributor.authorTong, Jen_US
dc.contributor.authorMa, Jen_US
dc.contributor.authorTang, Len_US
dc.contributor.authorYang, Xen_US
dc.contributor.authorShi, Yen_US
dc.contributor.authorTian, Jen_US
dc.contributor.authorLu, Len_US
dc.contributor.authorXu, Hen_US
dc.date.accessioned2012-05-29T06:14:13Z-
dc.date.available2012-05-29T06:14:13Z-
dc.date.issued2010en_US
dc.identifier.citationCellular And Molecular Immunology, 2010, v. 7 n. 4, p. 316-322en_US
dc.identifier.issn1672-7681en_US
dc.identifier.urihttp://hdl.handle.net/10722/148630-
dc.descriptionNature free article-
dc.description.abstractGlucocorticoid-induced tumor-necrosis factor receptor (GITR) and its ligand, GITRL, play significant roles in regulating immune responses. It is clear that human soluble GITRL (hsGITRL) transduces signal activity through multiple oligomerization states. To develop human soluble trimeric GITRL protein as a potential therapeutic target, we explored the link of the isoleucine-zipper (ILZ) motif to the N-terminus of the human soluble GITRL with two leucine sequences. hsGITRL, with the ILZ motif (ILZ-hsGITRL), was firstly expressed in Escherichia coli, which exhibited a predominant trimer when identified by Sephadex G-100 filtration and non-reducing SDS-polyacrylamide gel electrophoresis (SDS-PAGE). The significantly higher biological activity of the ILZ-hsGITRL compared with hsGITRL was confirmed by CD4 T proliferation, interferon-γ (IFN-γ) secretion and binding activity assay. To reveal and compare the underlying mechanisms, the level of extracellular signal-regulated kinase-1/2 (ERK1/2) phosphorylation was examined, indicating that ILZ-hsGITRL induced more persistent and stronger ERK1/2 activation than hsGITRL. In conclusion, the incorporation of an ILZ motif could markedly improve the costimulation of hsGITRL. © 2010 CSI and USTC. All rights reserved.en_US
dc.languageengen_US
dc.publisherChinese Society of Immunology. The Journal's web site is located at http://www.nature.com/cmi/index.htmlen_US
dc.relation.ispartofCellular and Molecular Immunologyen_US
dc.subjectGitr Liganden_US
dc.subjectIsoleucine Zipperen_US
dc.subjectT Cellsen_US
dc.titleAn isoleucine-zipper motif enhances costimulation of human soluble trimeric GITR liganden_US
dc.typeArticleen_US
dc.identifier.emailLu, L:liweilu@hkucc.hku.hken_US
dc.identifier.authorityLu, L=rp00477en_US
dc.description.naturelink_to_OA_fulltexten_US
dc.identifier.doi10.1038/cmi.2010.7en_US
dc.identifier.scopuseid_2-s2.0-77957264257en_US
dc.identifier.hkuros176939-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77957264257&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume7en_US
dc.identifier.issue4en_US
dc.identifier.spage316en_US
dc.identifier.epage322en_US
dc.identifier.isiWOS:000279487500011-
dc.publisher.placeChinaen_US

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