Signaling through a novel domain of gp130 mediates cell proliferation and activation of Hck and Erk kinases

Interleukin-6 (IL-6) induces the activation of the Src family kinase Hck, w hich is associated with the IL-6 receptor beta -chain, gp130. Here we descr ibe the identification of an "acidic" domain comprising amino acids 771 to 811 of gp130 as a binding region for Hck, which mediates proliferative sign aling. 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 pr oliferation upon stimulation of gp130 compared to wild-type gp130. In addit ion, 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, Er k, and Pyk2 and signals cell proliferation upon growth factor stimulation.