IL-13 INDUCES PHOSPHORYLATION AND ACTIVATION OF JAK2 JANUS KINASE IN HUMAN COLON-CARCINOMA CELL-LINES - SIMILARITIES BETWEEN IL-4 AND IL-13SIGNALING

We have recently reported that IL-13R may share a component with IL-4R , Here we report that both IL-4 and IL-13 share signaling events in hu man colon carcinoma cell lines (HT-29 and WiDr). IL-13 caused rapid ph osphorylation of the three out of four members of the known Janus fami ly of kinases (JAKs). We shaw that JAK2 kinase is rapidly phosphorylat ed and activated in response to IL-13, Within 1 min of activation, JAK 2 was phosphorylated, and peaked in 10 min. In addition, IL-13 phospho rylated insulin response substrate-1, IL-4R p140, JAK1, and Tyk2, but not JAK3 kinase. IL-4 also stimulated all three kinases and substrates , but unlike in immune cells, IL-4 did not involve JAK3 activation for its signaling in colon cancer cell lines, Furthermore, JAK2 associate d with the IL-4R p140 before and after stimulation with IL-13, Both IL -13 and IL-4 induced phosphorylation of IL-4 STAT (STAT6) but not STAT 1, STAT3, or STAT5, I-125-IL-13 did not bind to colon cancer cell line s, but unlabeled IL-13 competed for the binding of I-125-IL-4, Our dat a suggest that IL-13 utilizes IL-4R and its signaling pathway, and JAK 2 may play an important role in the function of IL-4R and IL-13R in co lon cancer cells.