JAK1 KINASE FORMS COMPLEXES WITH INTERLEUKIN-4 RECEPTOR AND 4PS INSULIN RECEPTOR SUBSTRATE-1-LIKE PROTEIN AND IS ACTIVATED BY INTERLEUKIN-4AND INTERLEUKIN-9 IN T-LYMPHOCYTES/

Interleukin (IL)-4 and IL-9 regulate the proliferation of T lymphocyte s through interactions with their receptors, Previous studies have sho wn that unknown tyrosine kinases are involved in the proliferative sig naling triggered by IL-4 and IL-9. Here we show that IL-4 and IL-9 ind uce overlapping (170, 130, and 125 kilodalton (kDa)) and distinct (45 and 88/90 kDa, respectively) protein tyrosine phosphorylation in T lym phocytes. We further identify the 170-kDa tyrosine-phosphorylated prot ein as 4PS/insulin receptor substrate-1-like (IRS-1L) protein and 130- kDa protein as JAK1 kinase. Furthermore, we demonstrate for the first time that JAK1 forms complexes with the IL-4 receptor and 4PS/IRS-1L p rotein following ligand-receptor interaction. In addition, we demonstr ate that IL-9, but not IL-4, induced tyrosine phosphorylation of Stat 91 transcriptional factor. The overlapping and distinct protein tyrosi ne phosphorylation and activation of the same JAK1 kinase in T lymphoc ytes strongly suggests that IL-4 and IL-9 share the common signal tran sduction pathways and that the specificity for each cytokine could be achieved through the unique tyrosine-phosphorylated proteins triggered by individual cytokines.