T cell receptor-mediated signal transduction controlled by the beta chain transmembrane domain: apoptosis-deficient cells display unbalanced mitogen-activated protein kinases activities upon T cell receptor engagement.
J Biol Chem
; 277(6): 3993-4002, 2002 Feb 08.
Article
em En
| MEDLINE
| ID: mdl-11724779
ABSTRACT
The bases that support the versatility of the T cell receptor (TCR) to generate distinct T cell responses remain unclear. We have previously shown that mutant cells in the transmembrane domain of TCRbeta chain are impaired in TCR-induced apoptosis but are not affected in other functions. Here we describe the biochemical mechanisms by which this mutant receptor supports some T cell responses but fails to induce apoptosis. Extracellular signal-regulated protein kinase (ERK) is activated at higher and more sustained levels in TCRbeta-mutated than in wild type cells. Conversely, activation of both c-Jun N-terminal kinase and p38 mitogen-activated protein kinase is severely reduced in mutant cells. By attempting to link this unbalanced induction to altered upstream events, we found that ZAP-70 is normally activated. However, although SLP-76 phosphorylation is normally induced, TCR engagement of mutant cells results in lower tyrosine phosphorylation of LAT but in higher tyrosine phosphorylation of Vav than in wild type cells. The results suggest that an altered signaling cascade leading to an imbalance in mitogen-activated protein kinase activities is involved in the selective impairment of apoptosis in these mutant cells. Furthermore, they also provide new insights in the contribution of TCR to decipher the signals that mediate apoptosis distinctly from proliferation.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores de Antígenos de Linfócitos T
/
Transdução de Sinais
/
Apoptose
/
Proteínas Quinases Ativadas por Mitógeno
Limite:
Humans
Idioma:
En
Revista:
J Biol Chem
Ano de publicação:
2002
Tipo de documento:
Article
País de afiliação:
Espanha