TUMOR-NECROSIS-FACTOR-ALPHA AND INTERLEUKIN-1 SIGNALING - DO MAPKK KINASES CONNECT IT ALL

The potent pro-inflammatory cytokines tumour necrosis factor alpha (TN F-alpha) and interleukin 1 (IL-l) are capable of triggering biological ly similar effects through activation of the same set of transcription factors. Based on recent findings it is now becoming evident that cer tain members of the mitogen-activated protein kinase kinase (MAPKK) ki nase protein family serve to integrate the individual signal transduct ion pathways that are initiated by the two cytokines into an array of parallel and common signalling cascades. The link between the receptor proximal, signal-specific intracellular events and the common MAPKK k inases appears to be made by a new class of proteins known as TNF rece ptor associated factors (TRAFs). Here, Jorg Eder describes how TNF-alp ha and IL-l use different, pathway-specific TRAFs to activate the same MAPKK kinase-controlled cascades.