Signaling through a Novel Domain of gp130 Mediates Cell Proliferation and Activation of Hck and Erk Kinases |
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| Authors: | Michael Schaeffer, Michaela Schneiderbauer, Sascha Weidler, Ros rio Tavares, Markus Warmuth, Gabriele de Vos, Michael Hallek |
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| Affiliation: | Medizinische Klinik III, Klinikum Grosshadern, Ludwig-Maximilians-Universit?t München, and Klinische Kooperationsgruppe Gentherapie, National Research Center for Health and Environment (GSF), D-81377 Munich, Germany. |
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| Abstract: | 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. |
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