Production of cytokines by IL-3-dependent mast cell lines in response to Fce receptor cross-linkage was demonstrated to involve tyrosine phosphorylation with cellular substrates. Moreover, when expression vectors containing tyrosine kinase receptors were introduced into an IL-3-dependent mast cell line, stimulation of these receptors with their respective ligands induced cytokine production by the mast cell transfectants. These results provide evidence that tyrosine kinase activation of intracellular substrates is crucial for the induction of cytokines by mast cells. Colony-stimulating factor-1 (CSF-1) was demonstrated to induce tyrosine phosphorylation of GAP and its associated cellular proteins p62 and p190 in NIH/3T3 cells overexpressing the human CSF-1 receptor. CSF-1 also increased the activation of p21ras, the extent of which correlated well with the mitogenic response induced by CSF-1. Taken together, these results provide evidence for a possible role of tyrosine phosphorylation of GAP and GAP-associated phosphoproteins in regulating transduction of CSF-1-induced mitogenic signals through p21ras activation. The effects of IL-4 on signal transduction in an IL-3 dependent myeloid progenitor line, FDCP-2, was examined and compared to those induced by IL-3. We demonstrate that IL-3 and IL-4 induce tyrosine phosphorylation of a distinct set of cellular substrates in this cell background, including certain known substrates such as PI-3 kinase and raf.
