ACTIVATION OF 12-O-TETRADECANOYLPHORBOL-13-ACETATE RESPONSE ELEMENT-DEPENDENT AND DYAD SYMMETRY ELEMENT-DEPENDENT TRANSCRIPTION BY INTERLEUKIN-5 IS MEDIATED BY JUN N-TERMINAL KINASE STRESS-ACTIVATED PROTEIN-KINASE KINASES

Interleukin-5 (IL-5) is one of the major regulators of eosinophilic gr anulocytes in vivo. IL-5 exerts its pleiotropic effects by binding to the IL-5 receptor, which is composed of an IL-5-specific alpha chain a nd a common beta c chain shared with the receptors for IL-5 and granul ocyte-macrophage colony-stimulating factor, Previous studies have show n that binding of IL-5 to its receptor triggers the activation of mult iple signaling cascades, including the Ras/mitogen-activated protein k inase, the phosphatidyl -3'-kinase, and the Janus kinase/signal transd ucer and activator of transcription pathways. Here we describe that IL -5 activates the serine/threonine protein kinase Jun N-terminal kinase /stress-activated protein kinase (JNK/SAPK) pathway. We show that IL-5 activates TPA response element (TRE)-dependent transcription in trans fection experiments. TRE activation by IL-5 is mediated by a region of the beta c (577-581) that is also responsible for activation of JNK/S APK and for activation of dyad symmetry element (DSE)-dependent transc ription. Dominant-negative SAPK or ERH kinase-1 was used to demonstrat e that JNK/SAPK activation is necessary for induction of DSE- and TRE- dependent transcription by IL-5, whereas extracellular signal-regulate d kinase 2 was not essential for TRE- and DSE-dependent transcription, By contrast, IL-5-induced activation of the tyrosine kinase Janus kin ase 2 seems to be a prerequisite for TRE- and DSE-dependent transcript ion. Taken together, we show for the first time that IL-5 activates ki nases of the JNK/SAPK family, and that this activation is linked to IL -5-induced TRE- and DSE-dependent transcription.