ACTIVATION OF THE SAPK PATHWAY BY THE HUMAN STE20 HOMOLOG GERMINAL CENTER KINASE

EUKARYOTIC cells respond to different extracellular stimuli by recruit ing homologous signalling pathways that use members of the MEKK, MEK a nd ERK families of protein kinases. The MEKK-->MEK-->ERK core pathways of Saccharomyces cerevisiae may themselves be regulated by members of the STE20 family of protein kinases(1,2). Here we report specific act ivation of the mammalian stress-activated protein kinase (SAPK) pathwa y by germinal centre kinase (GCK; ref. 3), a human STE20 homologue(3,4 ). SAPKs, members of the ERK family, are activated in situ by inflamma tory stimuli, including tumour-necrosis factor (TNF) and interleukin-1 , and phosphorylate and probably stimulate the transactivation functio n of c-Jun(5-7). Although GCK is found in many tissues, its expression in lymphoid follicles is restricted to the cells of the germinal cent re, where it may participate in B-cell differentiation(3). Activation of the SAPK pathway by GCK illustrates further the striking, conservat ion of eukaryotic signalling mechanisms and defines the first physiolo gical function of a mammalian Ste20.