CONSTITUTIVE ASSOCIATION OF JAK1 AND STAT5 IN PRO-B CELLS IS DISSOLVED BY INTERLEUKIN-4-INDUCED TYROSINE PHOSPHORYLATION OF BOTH PROTEINS

The bipartite human interleukin-4 (IL-4) receptor was functionally exp ressed in murine pro-B cells and activated by human IL-4 to evoke intr acellular signaling. Mutual association of signal transducing proteins within the receptor complex was then studied in dependence of ligand stimulation. Besides ligand-induced receptor heterodimerization and co ntacts of the two IL-4 receptor subunits alpha and gamma with Janus ki nases JAK1 and JAK3 a prominent constitutive binding between JAK1 and signal transducer and activator of transcription STAT5 was detected. S ince both these proteins become phosphorylated in response to IL-4 rec eptor stimulation, the influence of tyrosine phosphorylation on their mutual contact was analyzed. Association of JAK1 and STAT5 was found t o occur exclusively between unphosphorylated proteins. (C) 1998 Federa tion of European Biochemical Societies.