INTERLEUKIN-5 SIGNALING IN HUMAN EOSINOPHILS INVOLVES JAK2 TYROSINE KINASE AND STAT1-ALPHA

Signaling by a wide variety of cytokines, including interferons, inter leukins, and growth factors, involves activation of JAK kinases and St at (Signal transducers and activators of transcription) proteins. At p resent, not much is known about the molecular mechanisms by which inte rleukin-5 (IL-5) exerts its diverse biologic effects. Human eosinophil s are one of the most important target cells for IL-5 and were used he re to study IL-5 signaling in a primary human cell. IL-5 induced rapid and transient tyrosine phosphorylation of JAK2. Moreover, IL-5 induce d at least two DNA-binding complexes, using nuclear extracts from norm al human eosinophils and the IL-6/interferon-gamma response element of the ICAM-1 promotor (ICAM-1 pIRE) in an electromobility shift assay. From supershift experiments it was concluded that one DNA-binding comp lex contained Stat1 alpha, probably as a homodimer. Both DNA-binding c omplexes ware inhibited by a phosphotyrosine antibody (4G10), suggesti ng that tyrosine phosphorylation is required for complex formation. IL -3 and granulocyte-macrophage colony-stimulating factor induced, simil ar to IL-5, two DNA-binding complexes in human eosinophils, including Stat1 alpha. These data show for the first time that molecular mechani sms of IL-5 signaling in human eosinophils involve members of the JAK kinase family as well as members of the Stat family. (C) 1995 by The A merican Society of Hematology.