DIFFERENTIAL TYROSINE PHOSPHORYLATION OF JAK1, JAK2, AND STAT1 BY GROWTH-HORMONE AND INTERFERON-GAMMA IN IM-9 CELLS

Both the growth hormone (GH) and interferon gamma (IFN gamma) receptor s are members of the cytokine receptor family that activate tyrosine p hosphorylation despite the lack of a tyrosine kinase domain. Recently, the Janus kinase (JAK) family of tyrosine kinases have been shown to play an integral role in intracellular signaling by the cytokine recep tors. We demonstrate that, in the human IM-9 lymphocyte, both JAK1 and JAK2 are tyrosine-phosphorylated in response to IFN gamma, whereas on ly JAK2 is tyrosine-phosphorylated in response to GH. Furthermore, dim erization of the GH receptor appears to be necessary for GH stimulated tyrosine phosphorylation of JAK2. We provide two lines of evidence th at the JAK2 kinases can be regulated independently by GH and IFN gamma in IM-9 cells: 1) desensitization of JAK2 to GH stimulation does not affect the IFN gamma stimulated tyrosine phosphorylation of JAK2; and 2) JAK2 tyrosine phosphorylation by GH and IFN gamma is additive to th at seen with either hormone alone. Furthermore, we demonstrate that al though IFN gamma activates the tyrosine phosphorylation of the p91 sig nal transducer and activator of transcription (STAT1) in IM-9 cells, G H does not. GH does activate the tyrosine phosphorylation of a 93-kDa protein that appears to be distinct from STAT1.