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Originally published In Press as doi:10.1074/jbc.M011139200 on March 23, 2001

J. Biol. Chem., Vol. 276, Issue 23, 20022-20028, June 8, 2001
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Protein Kinase C theta  Cooperates with Vav1 to Induce JNK Activity in T-cells*

Andreas Möller, Oliver Dienz, Steffen P. Hehner, Wulf Dröge, and M. Lienhard SchmitzDagger

From the German Cancer Research Center, Division of Immunochemistry (G0200), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany

Here we show that in human T-cell leukemia cells Vav1 and protein kinase C theta  (PKCtheta ) synergize for the activation of c-Jun N-terminal kinase (JNK) but not p38 MAP kinase. Vav1 and PKCtheta also cooperated to induce transcription of reporter genes controlled either by AP-1 binding sites or the CD28RE/AP composite element contained in the IL-2 promoter by stimulating the binding of transcription factors to these two elements. Dominant negative versions of Vav1 and PKCtheta inhibited CD3/CD28-induced activation of JNK, revealing their relative importance for this activation pathway. Gel filtration experiments revealed the existence of constitutively associated Vav1/PKCtheta heterodimers in extracts from unstimulated T-cells, whereas T-cell costimulation induced the recruitment of Vav1 into high molecular weight complexes. Several experimental approaches showed that Vav1 is located upstream from PKCtheta in the control of the pathway leading to synergistic JNK activation. Vav1-derived signals lead to the activation of JNK by at least two different pathways. The major contribution of Vav1 for the activation of JNK relies on the PKCtheta -mediated Ca2+-independent synergistic activation pathway, whereas JNK is also activated by a separate Ca2+-dependent signaling route.


* This work was supported by grants from the Land Baden-Württemberg, European Union (QLK3-2000-00463), Fonds der Chemischen Industrie, Deutsche Forschungsgemeinschaft (Schm 1417/3-1), and Deutsche Krebshilfe.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger To whom correspondence should be addressed. Tel.: 49-6221-423725; Fax: 49-6221-423746; E-mail: L.Schmitz@DKFZ.de.


Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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