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The stress-activated protein kinase subfamily of c-Jun kinases

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Abstract

THE mitogen-activated protein (MAP) kinases Erk-1 and Erk-2 are proline-directed kinases that are themselves activated through concomitant phosphorylation of tyrosine and threonine residues1–4. The kinase p54 (Mr 54,000), which was first isolated from cycloheximide-treated rats, is proline-directed like Erks-1/2, and requires both Tyr and Ser/Thr phosphorylation3,5,6 for activity. p54 is, however, distinct from Erks-1/2 in its substrate specificity, being unable to phosphon late pp90rsk but more active in phosphor-ylating the c-Jun transactivation domain5,7,8. Molecular cloning of p54 reveals a unique subfamily of extracellularly regulated kinases. Although they are 40–45% identical in sequence to Erks-1/2, unlike Erks-1/2 the p54s are only poorly activated in most cells by mitogens or phorbol esters. However, p54s are the principal c-Jun N-terminal kinases activated by cellular stress and tumour necrosis factor (TNF)-α, hence they are designated stress-activated protein kinases, or SAPKs. SAPKs are also activated by sphingo-myelinase, which elicits a subset of cellular responses to TNF-α (ref. 9). SAPKs therefore define a new TNF-α and stress-activated signalling pathway, possibly initiated by sphingomyelin-based second messengers, which regulates the activity of c-Jun.

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Author information

Author notes

  1. Papia Banerjee

    Present address: Biotransplant Inc., Building 96, Charlestown Navy Yard, Charlestown, Massachusetts, 02129, USA

  2. Eleni Nikolakaki

    Present address: Laboratory of Biochemistry, University of Thessaloniki, Thes-saloniki, Greece

  3. Mir F. Ahmad

    Present address: Department of Medicine, King Faisal Hospital and Research Center, Riyadh, Saudi Arabia

  4. Tianang Dai, Elizabeth A. Rubie and James R. Woodgett: The Ontario Cancer Institute, Princess Margaret Hospital, 500 Sherbourne Street, Toronto, Ontario M4X 1K9, Canada

Authors and Affiliations

  1. Diabetes Research Laboratory, Medical Services, Massachusetts General Hospital East, 149 13th Street, Charlestown, Massachusetts, 02129, USA

    John M. Kyriakis, Papia Banerjee, Eleni Nikolakaki, Tianang Dai, Elizabeth A. Rubie, Mir F. Ahmad, Joseph Avruch & James R. Woodgett

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  1. John M. Kyriakis
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  7. Joseph Avruch
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  8. James R. Woodgett
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Kyriakis, J., Banerjee, P., Nikolakaki, E. et al. The stress-activated protein kinase subfamily of c-Jun kinases. Nature 369, 156–160 (1994). https://doi.org/10.1038/369156a0

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  • DOI: https://doi.org/10.1038/369156a0

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