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The small GTP-binding proteins Rac1 and Cdc42regulate the activity of the JNK/SAPK signaling pathway

Coso, Omar A., Chiariello, Mario, Yu, Jin-Chen, Teramoto, Hidemi, Crespo, Piero, Xu, Ningzhi, Miki, Toru, Silvio Gutkind, J.·1995·Cell
DOI 10.1016/s0092-8674(05)80018-2
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Abstract

c-Jun amino-terminal kinases (JNKs) and mitogen-activated protein kinases (MAPKs) are closely related; however, they are independently regulated by a variety of environmental stimuli. Although molecules linking growth factor receptors to MAPKs have been recently identified, little is known about pathways controlling JNK activation. Here, we show that in COS-7 cells, activated Ras effectively stimulates MAPK but poorly induces JNK activity. In contrast, mutationally activated Rac1 and Cdc42 GTPases potently activate JNK without affecting MAPK, and oncogenic guanine nucleotide exchange factors for these Rho-like proteins selectively stimulate JNK activity. Furthermore, expression of inhibitory molecules for Rho-related GTPases and dominant negative mutants of Rac1 and Cdc42 block JNK activation by oncogenic exchange factors or after induction by inflammatory cytokines and growth factors. Taken together, these findings strongly support a critical role for Rac1 and Cdc42 in controlling the JNK signaling pathway.

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Metadata

Authors
Coso, O. A., Chiariello, M., Yu, J.-C., Teramoto, H., Crespo, P., Xu, N., Miki, T., & Silvio Gutkind, J.
Venue
Cell
Publisher
Elsevier BV
Published
1995-06
Volume
81
Issue
7
Pages
1137-1146
ISSN
0092-8674
DOI
10.1016/s0092-8674(05)80018-2
Cited by
1,397
References
3
Language
en
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CoChat. (2026). Citation check: The small GTP-binding proteins Rac1 and Cdc42regulate the activity of the JNK/SAPK signaling pathway. https://app.cochat.ai/papers/10.1016/s0092-8674(05)80018-2
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Coso, O. A., Chiariello, M., Yu, J.-C., Teramoto, H., Crespo, P., Xu, N., Miki, T., & Silvio Gutkind, J. (1995). The small GTP-binding proteins Rac1 and Cdc42regulate the activity of the JNK/SAPK signaling pathway. Cell. https://doi.org/10.1016/s0092-8674(05)80018-2