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J. Biol. Chem., Vol. 277, Issue 6, 3993-4002, February 8, 2002

This Article Full Text Full Text (PDF) All Versions of this Article: 277/6/3993    most recent M107797200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Teixeiro, E. Articles by Bragado, R. Search for Related Content PubMed PubMed Citation Articles by Teixeiro, E. Articles by Bragado, R. Social Bookmarking                      What's this?

T Cell Receptor-mediated Signal Transduction Controlled by the  Chain Transmembrane Domain
APOPTOSIS-DEFICIENT CELLS DISPLAY UNBALANCED MITOGEN-ACTIVATED PROTEIN KINASES ACTIVITIES UPON T CELL RECEPTOR ENGAGEMENT^*

Emma Teixeiro^§, Patricia Fuentes^§, Begoña Galocha^¶, Balbino Alarcón, and Rafael Bragado^**

From the  Department of Immunology, Fundación Jiménez Díaz, Avenida. Reyes Católicos 2, 28040 Madrid, Spain, the ^¶ Hospital Clínico San Carlos, Unidad de Investigación, Profesor Martín Lagos s/n, 28040 Madrid, Spain, and the  Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Cantoblanco, 28049 Madrid, Spain

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 TCR 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 TCR-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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