Publication Date:
1998-12-18
Description:
CTLA-4, a negative regulator of T cell function, was found to associate with the T cell receptor (TCR) complex zeta chain in primary T cells. The association of TCRzeta with CTLA-4, reconstituted in 293 transfectants, was enhanced by p56(lck)-induced tyrosine phosphorylation. Coexpression of the CTLA-4-associated tyrosine phosphatase, SHP-2, resulted in dephosphorylation of TCRzeta bound to CTLA-4 and abolished the p56(lck)-inducible TCRzeta-CTLA-4 interaction. Thus, CTLA-4 inhibits TCR signal transduction by binding to TCRzeta and inhibiting tyrosine phosphorylation after T cell activation. These findings have broad implications for the negative regulation of T cell function and T cell tolerance.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, K M -- Chuang, E -- Griffin, M -- Khattri, R -- Hong, D K -- Zhang, W -- Straus, D -- Samelson, L E -- Thompson, C B -- Bluestone, J A -- P01 AI35294-6/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 1998 Dec 18;282(5397):2263-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Ben May Institute for Cancer Research, and Committee on Immunology, University of Chicago, Chicago, IL 60637, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9856951" target="_blank"〉PubMed〈/a〉
Keywords:
Abatacept
;
Animals
;
Antigens, CD
;
Antigens, Differentiation/*metabolism
;
CTLA-4 Antigen
;
Cell Line
;
Cells, Cultured
;
Humans
;
*Immunoconjugates
;
Intracellular Signaling Peptides and Proteins
;
*Lymphocyte Activation
;
Lymphocyte Specific Protein Tyrosine Kinase p56(lck)/genetics/metabolism
;
Membrane Proteins/*metabolism
;
Mice
;
Mice, Inbred BALB C
;
Models, Immunological
;
Phosphorylation
;
Phosphotyrosine/metabolism
;
Protein Tyrosine Phosphatase, Non-Receptor Type 11
;
Protein Tyrosine Phosphatase, Non-Receptor Type 6
;
Protein Tyrosine Phosphatases/genetics/metabolism
;
Receptors, Antigen, T-Cell/*metabolism
;
Recombinant Fusion Proteins/metabolism
;
SH2 Domain-Containing Protein Tyrosine Phosphatases
;
*Signal Transduction
;
T-Lymphocytes/*immunology
;
Transfection
;
src Homology Domains
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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