INTERLEUKIN-4 INDUCES ACTIVATION OF MITOGEN-ACTIVATED PROTEIN-KINASE AND PHOSPHORYLATION OF SHC IN HUMAN KERATINOCYTES

Most cytokines stimulate the p21(ras) pathway, leading to MAP kinase a ctivation. One exception is interleukin-4 (IL-4), which has been shown not to activate this pathway in hematopoietic cells. However, IL-4 ac ts on a broad range of cells, including keratinocytes, in which it ind uces IL-6 production. We report here that IL-4 stimulation of human ke ratinocytic cell lines or primary cultures activates MAP kinase. In th ese cells, IL-4 stimulation induces the tyrosine phosphorylation of p4 2/44 MAP kinase as well as its catalytic activity, We also observed an increased phosphorylation of p46(shc), an SH2-containing protein invo lved in the Pas pathway, as a result of IL-4 stimulation in human kera tinocytic cell lines but not in T lymphocytes.