Activation of the SAPK pathway by the human STE20 homologue germinal centre kinase

Celia M. Pombo, John H. Kehrl, Irma Sánchez, Paul Katz, Joseph Avruch, Leonard I. Zon, James R. Woodgett, Thomas Force, John M. Kyriakis

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Abstract

Eukaryotic cells respond to different extracellular stimuli by recruiting homologous signalling pathways that use members of the MEKK, MEK and 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. Here we report specific activation of the mammalian stress-activated protein kinase (SAPK) pathway by germinal centre kinase (CGK), a human STE20 homologue, SAPKs, members of the ERK family, are activated n situ by inflammatory stimuli, including tumour-necrosis factor (TNF) and interleukin-1, and phosphorylate and probably stimulate the transactivation function of c-Jun. Although GCK is found in manly tissues, its expression in lymphoid follicles is restricted to the cells of the germinal centre, where it may participate in B-cell differentiation. Activation of the SAPK pathway by GCK illustrates further the striking conservation of eukaryotic signalling mechanisms and defines the first physiological function of a mammalian Ste20.

Original languageEnglish (US)
Pages (from-to)750-754
Number of pages5
JournalNature
Volume377
Issue number6551
DOIs
StatePublished - Jan 1 1995

ASJC Scopus subject areas

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    Pombo, C. M., Kehrl, J. H., Sánchez, I., Katz, P., Avruch, J., Zon, L. I., Woodgett, J. R., Force, T., & Kyriakis, J. M. (1995). Activation of the SAPK pathway by the human STE20 homologue germinal centre kinase. Nature, 377(6551), 750-754. https://doi.org/10.1038/377750a0