Activation of the SAPK pathway by the human STE20 homologue germinal centre kinase (original) (raw)
- Letter
- Published: 26 October 1995
- John H. Kehrl3,
- Irma Sánchez1,
- Paul Katz4,
- Joseph Avruch1,
- Leonard I. Zon5,
- James R. Woodgett6,
- Thomas Force2 &
- …
- John M. Kyriakis1
Nature volume 377, pages 750–754 (1995)Cite this article
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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 cere-visiae may themselves be regulated by members of the STE20 family of protein kinases1,2. Here we report specific activation of the mammalian stress-activated protein kinase (SAPK) pathway by germinal centre kinase (GCK; ref. 3), a human STE20 homologue3,4. SAPKs, members of the ERK family, are activated in situ by inflammatory stimuli, including tumour-necrosis factor (TNF) and interleukin-1, and phosphorylate and probably stimulate the transactivation function 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 centre, where it may participate in B-cell differentiation3. 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.
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Authors and Affiliations
- Diabetes Research Laboratory, Massachusetts General Hospital East and Department of Medicine, Harvard Medical School, 149 13th Street, Charlestown, Massachusetts, 02129, USA
Irma Sánchez, Joseph Avruch & John M. Kyriakis - Cardiology Unit, Massachusetts General Hospital East and Department of Medicine, Harvard Medical School, 149 13th Street, Charlestown, Massachusetts, 02129, USA
Celia M. Pombo & Thomas Force - Laboratory of Immunoregulation, NIAID, National Institutes of Health, Building 10, 10 Center Drive MSC 1876, Bethesda, Maryland, 20892, USA
John H. Kehrl - Department of Medicine, Georgetown University Medical Center, Washington, DC, 20007, USA
Paul Katz - Howard Hughes Medical Institute and Division of Hematology/ Oncology, Children's Hospital and Dana Farber Cancer Institute, Harvard Medical School, Enders 650, 300 Longwood Avenue, Boston, Massachusetts, 02115, USA
Leonard I. Zon - Ontario Cancer Institute, Princess Margaret Hospital, 500 Sherbourne Street, Toronto, Ontario, M4X 1K9, Canada
James R. Woodgett
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Pombo, C., Kehrl, J., Sánchez, I. et al. Activation of the SAPK pathway by the human STE20 homologue germinal centre kinase.Nature 377, 750–754 (1995). https://doi.org/10.1038/377750a0
- Received: 18 April 1995
- Accepted: 07 September 1995
- Issue Date: 26 October 1995
- DOI: https://doi.org/10.1038/377750a0