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Article: An isoleucine-zipper motif enhances costimulation of human soluble trimeric GITR ligand
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TitleAn isoleucine-zipper motif enhances costimulation of human soluble trimeric GITR ligand
 
AuthorsCui, D1 3
Wang, S1
Chen, Y3
Tong, J1
Ma, J1
Tang, L1
Yang, X1
Shi, Y1
Tian, J1
Lu, L2
Xu, H1
 
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
 
CitationCellular And Molecular Immunology, 2010, v. 7 n. 4, p. 316-322 [How to Cite?]
DOI: http://dx.doi.org/10.1038/cmi.2010.7
 
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.
 
ISSN1672-7681
2012 Impact Factor: 3.419
 
DOIhttp://dx.doi.org/10.1038/cmi.2010.7
 
ISI Accession Number IDWOS:000279487500011
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.

 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorCui, D
 
dc.contributor.authorWang, S
 
dc.contributor.authorChen, Y
 
dc.contributor.authorTong, J
 
dc.contributor.authorMa, J
 
dc.contributor.authorTang, L
 
dc.contributor.authorYang, X
 
dc.contributor.authorShi, Y
 
dc.contributor.authorTian, J
 
dc.contributor.authorLu, L
 
dc.contributor.authorXu, H
 
dc.date.accessioned2012-05-29T06:14:13Z
 
dc.date.available2012-05-29T06:14:13Z
 
dc.date.issued2010
 
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.
 
dc.description.natureLink_to_subscribed_fulltext
 
dc.identifier.citationCellular And Molecular Immunology, 2010, v. 7 n. 4, p. 316-322 [How to Cite?]
DOI: http://dx.doi.org/10.1038/cmi.2010.7
 
dc.identifier.doihttp://dx.doi.org/10.1038/cmi.2010.7
 
dc.identifier.epage322
 
dc.identifier.isiWOS:000279487500011
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.

 
dc.identifier.issn1672-7681
2012 Impact Factor: 3.419
 
dc.identifier.issue4
 
dc.identifier.scopuseid_2-s2.0-77957264257
 
dc.identifier.spage316
 
dc.identifier.urihttp://hdl.handle.net/10722/148630
 
dc.identifier.volume7
 
dc.languageeng
 
dc.publisherChinese Society of Immunology. The Journal's web site is located at http://www.nature.com/cmi/index.html
 
dc.publisher.placeChina
 
dc.relation.ispartofCellular and Molecular Immunology
 
dc.relation.referencesReferences in Scopus
 
dc.subjectGitr Ligand
 
dc.subjectIsoleucine Zipper
 
dc.subjectT Cells
 
dc.titleAn isoleucine-zipper motif enhances costimulation of human soluble trimeric GITR ligand
 
dc.typeArticle
 
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<contributor.author>Tong, J</contributor.author>
<contributor.author>Ma, J</contributor.author>
<contributor.author>Tang, L</contributor.author>
<contributor.author>Yang, X</contributor.author>
<contributor.author>Shi, Y</contributor.author>
<contributor.author>Tian, J</contributor.author>
<contributor.author>Lu, L</contributor.author>
<contributor.author>Xu, H</contributor.author>
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Author Affiliations
  1. Jiangsu University
  2. The University of Hong Kong
  3. Zhejiang University