| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Institute of Molecular and Clinical Immunology and
Department of Dermatology and Venerology, Otto-von-Guericke-University, Magdeburg; and
Max-Planck-Institute for Dynamics of Complex Technical Systems, Magdeburg, Germany
Engagement of the TCR can induce different functional outcomes such as activation, proliferation, survival, or apoptosis. How the TCR-mediated signaling cascades generating these distinct cellular responses are organized on the molecular level is so far not completely understood. To obtain insight into this question, we analyzed TCR/CD8-mediated signaling events in mature OT-I TCR transgenic T cells under conditions of stimulation that lead to either proliferation or apoptosis. These experiments revealed major differences in the phosphorylation dynamics of LAT, ZAP70, protein kinase B, phospholipase C-
1, protein kinase D1, and ERK1/2. Moreover, input signals leading to apoptosis induced a strong, but transient activation of ERK1/2 mainly at sites of TCR-engagement. In contrast, stimuli promoting survival/proliferation generated a low and sustained activation of ERK1/2, which colocalizes with Ras in recycling endosomal vesicles. The transient activation of ERK1/2 under pro-apoptotic conditions of stimulation is at least partially due to the rapid polyubiquitination and subsequent degradation of ZAP70, whereas the sustained activation of ERK1/2 under survival promoting conditions is paralleled by the induction/phosphorylation of anti-apoptotic molecules such as protein kinase B and Bcl-xL. Collectively, our data provide signaling signatures that are associated with proliferation or apoptosis of T cells.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by grants from the German Research Foundation to B. S. and S. K. (FOR521 and GRK1167).
2 Address correspondence and reprint requests to Dr. Burkhart Schraven and Dr. Stefanie Kliche, Institute of Molecular and Clinical Immunology, Otto-von-Guericke-University, Leipziger Strasse 44, D-39120 Magdeburg, Germany. E-mail addresses: burkhart.schraven{at}med.ovgu.de and stefanie.kliche{at}med.ovgu.de
3 Abbreviations used in this paper: DAG, diacylglycerol; WT, wild type; tg, transgenic; p, phospho; PI, propidium iodide; PKB, protein kinase B; PKD1, protein kinase D1.
Related articles in The JI:
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
