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Science 10 January 1997:
Vol. 275. no. 5297, pp. 200 - 203
DOI: 10.1126/science.275.5297.200
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Reports

Activation of SAPK/JNK by TNF Receptor 1 Through a Noncytotoxic TRAF2-Dependent Pathway

Gioacchino Natoli, * Antonio Costanzo, Angelo Ianni, Dennis J. Templeton, James R. Woodgett, Clara Balsano, Massimo Levrero

Interaction of the p55 tumor necrosis factor receptor 1 (TNF-R1)-associated signal transducer TRADD with FADD signals apoptosis, whereas the TNF receptor-associated factor 2 protein (TRAF2) is required for activation of the nuclear transcription factor nuclear factor kappa B. TNF-induced activation of the stress-activated protein kinase (SAPK) was shown to occur through a noncytotoxic TRAF2-dependent pathway. TRAF2 was both sufficient and necessary for activation of SAPK by TNF-R1; conversely, expression of a dominant-negative FADD mutant, which blocks apoptosis, did not interfere with SAPK activation. Therefore, SAPK activation occurs through a pathway that is not required for TNF-R1-induced apoptosis.

G. Natoli, A. Costanzo, A. Ianni, M. Levrero, Fondazione Andrea Cesalpino and Istituto di I Clinica Medica, Policlinico Umberto I, Viale del Policlinico 155, 00161 Rome, Italy.
D. J. Templeton, Case Western Reserve University School of Medicine, Biomedical Research Building, Cleveland, OH 44106, USA.
J. R. Woodgett, Ontario Cancer Institute-Princess Margaret Hospital, Toronto M5G 2M9, Canada.
C. Balsano, Dipartimento di Medicina Interna, Università di L'Aquila, L'Aquila, 67100, Italy.
*   To whom correspondence should be addressed.

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Nuclear Factor kB-independent Cytoprotective Pathways Originating at Tumor Necrosis Factor Receptor-associated Factor 2.
G. Natoli, A. Costanzo, F. Guido, F. Moretti, A. Bernardo, V. L. Burgio, C. Agresti, and M. Levrero (1998)
J. Biol. Chem. 273, 31262-31272
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Analysis of Human Breast Adenocarcinoma MCF7 Resistance to Tumor Necrosis Factor-induced Cell Death. LACK OF CORRELATION BETWEEN JNK ACTIVATION AND CERAMIDE PATHWAY.
M. Ameyar, A. Atfi, Z. Cai, R. Stancou, V. Shatrov, A. Bettaieb, and S. Chouaib (1998)
J. Biol. Chem. 273, 29002-29008
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Role of the TRAF Binding Site and NF-kappa B Activation in Epstein-Barr Virus Latent Membrane Protein 1-Induced Cell Gene Expression.
O. Devergne, E. C. McFarland, G. Mosialos, K. M. Izumi, C. F. Ware, and E. Kieff (1998)
J. Virol. 72, 7900-7908
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I. TNF-induced liver injury.
C. A. Bradham, J. Plumpe, M. P. Manns, D. A. Brenner, and C. Trautwein (1998)
Am J Physiol Gastrointest Liver Physiol 275, G387-G392
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Tumor Necrosis Factor Signaling to Stress-activated Protein Kinase (SAPK)/Jun NH2-terminal Kinase (JNK) and p38. GERMINAL CENTER KINASE COUPLES TRAF2 TO MITOGEN-ACTIVATED PROTEIN KINASE/ERK KINASE KINASE 1 AND SAPK WHILE RECEPTOR INTERACTING PROTEIN ASSOCIATES WITH A MITOGEN-ACTIVATED PROTEIN KINASE KINASE KINASE UPSTREAM OF MKK6 AND p38.
T. Yuasa, S. Ohno, J. H. Kehrl, and J. M. Kyriakis (1998)
J. Biol. Chem. 273, 22681-22692
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Cooperative Signaling by Tumor Necrosis Factor Receptors CD120a (p55) and CD120b (p75) in the Expression of Nitric Oxide and Inducible Nitric Oxide Synthase by Mouse Macrophages.
D. W. H. Riches, E. D. Chan, E. A. Zahradka, B. W. Winston, L. K. Remigio, and F. R. Lake (1998)
J. Biol. Chem. 273, 22800-22806