The stress-activated protein kinase subfamily of c-Jun kinases (original) (raw)

• Letter
• Published: 12 May 1994
• Papia Banerjee1 nAff3,
• Eleni Nikolakaki1 nAff4,
• Tianang Dai1 na1,
• Elizabeth A. Rubie1 na1,
• Mir F. Ahmad1 nAff5,
• Joseph Avruch1 &
• …
• James R. Woodgett1 na1

Nature volume 369, pages 156–160 (1994)Cite this article

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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 pp90_rsk_ 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 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

Authors

1. John M. Kyriakis
2. Papia Banerjee
3. Eleni Nikolakaki
4. Tianang Dai
5. Elizabeth A. Rubie
6. Mir F. Ahmad
7. Joseph Avruch
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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• Received: 17 January 1994
• Accepted: 05 April 1994
• Issue date: 12 May 1994
• DOI: https://doi.org/10.1038/369156a0