Activation of the SAPK pathway by the human STE20 homologue germinal centre kinase (original) (raw)

Nature volume 377, pages 750–754 (1995)Cite this article

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

  1. 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
  2. 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
  3. Laboratory of Immunoregulation, NIAID, National Institutes of Health, Building 10, 10 Center Drive MSC 1876, Bethesda, Maryland, 20892, USA
    John H. Kehrl
  4. Department of Medicine, Georgetown University Medical Center, Washington, DC, 20007, USA
    Paul Katz
  5. 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
  6. Ontario Cancer Institute, Princess Margaret Hospital, 500 Sherbourne Street, Toronto, Ontario, M4X 1K9, Canada
    James R. Woodgett

Authors

  1. Celia M. Pombo
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  2. John H. Kehrl
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  3. Irma Sánchez
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  4. Paul Katz
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  5. Joseph Avruch
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  6. Leonard I. Zon
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  7. James R. Woodgett
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  8. Thomas Force
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  9. John M. Kyriakis
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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

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