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Titolo:
THE JNK PATHWAY REGULATES THE IN-VIVO DELETION OF IMMATURE CD4(+)CD8(+) THYMOCYTES
Autore:
RINCON M; WHITMARSH A; YANG DD; WEISS L; DERIJARD B; JAYARAJ P; DAVIS RJ; FLAVELL RA;
Indirizzi:
YALE UNIV,SCH MED,IMMUNOBIOL SECT,310 CEDAR ST,FMB 412 NEW HAVEN CT 06520 YALE UNIV,SCH MED,IMMUNOBIOL SECT NEW HAVEN CT 06520 UNIV VERMONT,DEPT MED,IMMUNOBIOL PROGRAM BURLINGTON VT 05405 HOWARD HUGHES MED INST NEW HAVEN CT 06520 UNIV MASSACHUSETTS,SCH MED,DEPT BIOCHEM & MOL BIOL,PROGRAM MOL MED WORCESTER MA 01605 HOWARD HUGHES MED INST WORCESTER MA 01605 CTR BIOCHIM,UMR 134 F-06108 NICE 2 FRANCE
Titolo Testata:
The Journal of experimental medicine
fascicolo: 10, volume: 188, anno: 1998,
pagine: 1817 - 1830
SICI:
0022-1007(1998)188:10<1817:TJPRTI>2.0.ZU;2-S
Fonte:
ISI
Lingua:
ENG
Soggetto:
ACTIVATED PROTEIN-KINASE; AP-1 TRANSCRIPTIONAL ACTIVITY; JUN NH2-TERMINAL KINASE; GTP EXCHANGE FACTOR; NEGATIVE SELECTION; T-CELLS; INDUCED APOPTOSIS; C-JUN; POSITIVE SELECTION; THYMIC SELECTION;
Keywords:
T LYMPHOCYTE; JNK; THYMIC DEVELOPMENT; APOPTOSIS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
69
Recensione:
Indirizzi per estratti:
Citazione:
M. Rincon et al., "THE JNK PATHWAY REGULATES THE IN-VIVO DELETION OF IMMATURE CD4(+)CD8(+) THYMOCYTES", The Journal of experimental medicine, 188(10), 1998, pp. 1817-1830

Abstract

The extracellular signal-regulated kinase (ERK), the c-Jun NH2-terminal kinase (JNK), and p38 MAP kinase pathways are triggered upon ligation of the antigen-specific T cell receptor (TCR). During the development of I cells in the thymus, the ERK pathway is required for differentiation of CD4(-)CD8(-) into CD4(+)CD8(+) double positive (DP) thymocytes, positive selection of DP cells, and their maturation into CD4(+) cells. However, the ERK pathway is not required for negative selection. Here, we show that JNK is activated in DP thymocytes in vivo in response to signals that initiate negative selection. The activation of JNKin these cells appears to be mediated by the MAP kinase kinase MKK7 since high levels of MKK7 and low levels of Sek-1/MKK4 gene expression were detected in thymocytes. Using dominant negative JNK transgenic mice, we show that inhibition of the JNK pathway reduces the in vivo deletion of DP thymocytes. In addition, the increased resistance of DP thymocytes to cell death in these mice produces an accelerated reconstitution of normal thymic populations upon in vivo DP elimination. Together, these data indicate that the JNK pathway contributes to the deletion of DP thymocytes by apoptosis in response to TCR-derived and other thymic environment-mediated signals.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 27/11/20 alle ore 04:45:24