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Molecular and Cellular Biology, December 2001, p. 8068-8081, Vol. 21, No. 23
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.23.8068-8081.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Signaling through a Novel Domain of gp130 Mediates Cell Proliferation and Activation of Hck and Erk Kinases

Michael Schaeffer, Michaela Schneiderbauer, Sascha Weidler, Rosário Tavares, Markus Warmuth, Gabriele de Vos, and Michael Hallek*

Medizinische Klinik III, Klinikum Grosshadern, Ludwig-Maximilians-Universität München, and Klinische Kooperationsgruppe Gentherapie, National Research Center for Health and Environment (GSF), D-81377 Munich, Germany

Received 1 June 2001/Returned for modification 19 July 2001/Accepted 16 August 2001

Interleukin-6 (IL-6) induces the activation of the Src family kinase Hck, which is associated with the IL-6 receptor beta -chain, gp130. Here we describe the identification of an "acidic" domain comprising amino acids 771 to 811 of gp130 as a binding region for Hck, which mediates proliferative signaling. The deletion of this region of gp130 (i.e., in deletion mutant d771-811) resulted in a significant reduction of Hck kinase activity and cell proliferation upon stimulation of gp130 compared to wild-type gp130. In addition, d771-811 disrupted the growth factor-stimulated activation of Erk and the dephosphorylation of Pyk2. Based on these findings, we propose a novel, acidic domain of gp130, which is responsible for the activation of Hck, Erk, and Pyk2 and signals cell proliferation upon growth factor stimulation.


* Corresponding author. Mailing address: GSF-KKG Gentherapie, Marchioninistr. 25, D-81377 Munich, Germany. Phone: 49-89-7095-3038. Fax: 49-89-2180-6797. E-mail: michael.hallek{at}med3.med.uni-muenchen.de.


Molecular and Cellular Biology, December 2001, p. 8068-8081, Vol. 21, No. 23
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.23.8068-8081.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.



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