Publication Date:
1997-10-06
Description:
In the absence of costimulation, T cells activated through their antigen receptor become unresponsive (anergic) and do not transcribe the gene encoding interleukin-2 (IL-2) when restimulated with antigen. Anergic alloantigen-specific human T cells contained phosphorylated Cbl that coimmunoprecipitated with Fyn. The adapter protein CrkL was associated with both phosphorylated Cbl and the guanidine nucleotide-releasing factor C3G, which catalyzes guanosine triphosphate (GTP) exchange on Rap1. Active Rap1 (GTP-bound form) was present in anergic cells. Forced expression of low amounts of Rap1-GTP in Jurkat T cells recapitulated the anergic defect and blocked T cell antigen receptor (TCR)- and CD28-mediated IL-2 gene transcription. Therefore, Rap1 functions as a negative regulator of TCR-mediated IL-2 gene transcription and may be responsible for the specific defect in IL-2 production in T cell anergy.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Boussiotis, V A -- Freeman, G J -- Berezovskaya, A -- Barber, D L -- Nadler, L M -- AI 35225/AI/NIAID NIH HHS/ -- AI39671/AI/NIAID NIH HHS/ -- HL 54785/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1997 Oct 3;278(5335):124-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Adult Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA. vassiliki_boussiotis@macmailgw.dfci.harvard.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9311917" target="_blank"〉PubMed〈/a〉
Keywords:
*Adaptor Proteins, Signal Transducing
;
Antigens, CD28/immunology
;
*Clonal Anergy
;
GTP-Binding Proteins/*metabolism
;
Gene Expression Regulation
;
Guanine Nucleotide Exchange Factors
;
Guanosine Triphosphate/metabolism
;
Humans
;
Interleukin-2/*genetics
;
Jurkat Cells
;
Nuclear Proteins/metabolism
;
Phosphorylation
;
Protein-Tyrosine Kinases/metabolism
;
Proteins/metabolism
;
Proto-Oncogene Proteins/metabolism
;
Proto-Oncogene Proteins c-cbl
;
Proto-Oncogene Proteins c-fyn
;
Receptors, Antigen, T-Cell/immunology
;
Recombinant Fusion Proteins/metabolism
;
Signal Transduction
;
T-Lymphocytes/*immunology/metabolism
;
*Transcription, Genetic
;
Transfection
;
*Ubiquitin-Protein Ligases
;
rap GTP-Binding Proteins
;
ras Guanine Nucleotide Exchange Factors
;
ras Proteins/metabolism
;
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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