ABERRANT ACTIVATION OF JAK STAT PATHWAY COMPONENTS IN RESPONSE TO G-CSF, INTERFERON-ALPHA/BETA AND INTERFERON-GAMMA IN NFS-60 CELLS/

There is evidence that the cellular responses to cytokines, such as gr anulocyte colony stimulating factor (G-CSF) and interferons, depend on prior activation of components of the JAK/STAT signalling pathway. We report here that the myeloid cell line NFS-60 shows aberrant JAK/STAT signalling yet elicits expected biological responses to G-CSF and int erferons-alpha/beta and gamma. Instead of increased phosphorylation of JAK1 and JAK2 in response to G-CSF and interferon-gamma, and JAK1 and Tyk2 in response to interferon-alpha/beta, we observed only an increa se of phosphorylation of Tyk2 in response to all of these cytokines in NFS-60 cells. The subset of STAT proteins being activated in response to these cytokines was unusual as well. G-CSF activated STAT3 and STA T5A, whereas interferons activated, in addition to STAT1 and STAT5 oth er, as yet unidentified, DNA binding proteins. However, NFS-60 cells s how normal biological responses to these cytokines, such as proliferat ion in response to G-CSF, and reduction of proliferation, induction of an anti-viral response and induction of specific genes in response to interferons.