Interleukin-4 induces activation of mitogen-activated protein kinase and phosphorylation of shc in human keratinocytes

Most cytokines stimulate the p21ras pathway, leading to MAP kinase activation. One exception is interleukin-4 (IL-4), which has been shown not to activate this pathway in hematopoietic cells. However, IL-4 acts on a broad range of cells, including keratinocytes, in which it induces IL-6 production. We report here that IL-4 stimulation of human keratinocytic cell lines or primary cultures activates MAP kinase. In these cells, IL-4 stimulation induces the tyrosine phosphorylation of p42/44 MAP kinase as well as its catalytic activity. We also observed an increased phosphorylation of p46shc, an SH2-containing protein involved in the Ras pathway, as a result of IL-4 stimulation in human keratinocytic cell lines but not in T lymphocytes.