Document Detail

Caveolin-1 triggers T-cell activation via CD26 in association with CARMA1.
MedLine Citation:
PMID:  17287217     Owner:  NLM     Status:  MEDLINE    
CD26 is a widely distributed 110-kDa cell surface glycoprotein with an important role in T-cell costimulation. We demonstrated previously that CD26 binds to caveolin-1 in antigen-presenting cells, and following exogenous CD26 stimulation, Tollip and IRAK-1 disengage from caveolin-1 in antigen-presenting cells. IRAK-1 is then subsequently phosphorylated to up-regulate CD86 expression, resulting in subsequent T-cell proliferation. However, it is unclear whether caveolin-1 is a costimulatory ligand for CD26 in T-cells. Using soluble caveolin-1-Fc fusion protein, we now show that caveolin-1 is the costimulatory ligand for CD26, and that ligation of CD26 by caveolin-1 induces T-cell proliferation and NF-kappaB activation in a T-cell receptor/CD3-dependent manner. We also demonstrated that the cytoplasmic tail of CD26 interacts with CARMA1 in T-cells, resulting in signaling events that lead to NF-kappaB activation. Ligation of CD26 by caveolin-1 recruits a complex consisting of CD26, CARMA1, Bcl10, and IkappaB kinase to lipid rafts. Taken together, our findings provide novel insights into the regulation of T-cell costimulation via the CD26 molecule.
Kei Ohnuma; Masahiko Uchiyama; Tadanori Yamochi; Kunika Nishibashi; Osamu Hosono; Nozomu Takahashi; Shinichiro Kina; Hirotoshi Tanaka; Xin Lin; Nam H Dang; Chikao Morimoto
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-02-06
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  282     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2007 Mar 
Date Detail:
Created Date:  2007-03-26     Completed Date:  2007-05-10     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  10117-31     Citation Subset:  IM    
Division of Clinical Immunology, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
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MeSH Terms
Adenosine Deaminase / physiology*
Antigens, CD26 / physiology*
Apoptosis Regulatory Proteins / physiology*
CARD Signaling Adaptor Proteins / physiology*
Caveolin 1 / physiology*
Glycoproteins / physiology*
Guanylate Cyclase / physiology*
Jurkat Cells
Lymphocyte Activation / immunology*
Signal Transduction / physiology*
T-Lymphocytes / immunology,  metabolism*
Reg. No./Substance:
0/Apoptosis Regulatory Proteins; 0/CARD Signaling Adaptor Proteins; 0/CAV1 protein, human; 0/Caveolin 1; 0/Glycoproteins; EC, CD26; EC protein, human; EC Deaminase; EC protein, human; EC Cyclase

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