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Mechanism of p38 MAP kinase activation in vivo

Open access
Brancho, Deborah, Tanaka, Nobuyuki, Jaeschke, Anja, Ventura, Juan-Jose, Kelkar, Nyaya, Tanaka, Yoshinori, Kyuuma, Masanao, Takeshita, Toshikazu, Flavell, Richard A., Davis, Roger J.·2003·Genes & Development

Abstract

The p38 mitogen-activated protein kinase (MAPK) is activated in vitro by three different protein kinases: MKK3, MKK4, and MKK6. To examine the relative roles of these protein kinases in the mechanism of p38 MAP kinase activation in vivo, we examined the effect of disruption of the murine Mkk3, Mkk4 , and Mkk6 genes on the p38 MAPK signaling pathway. We show that MKK3 and MKK6are essential for tumor necrosis factor-stimulated p38 MAPK activation. In contrast, ultraviolet radiation-stimulated p38 MAPK activation was mediated by MKK3, MKK4, and MKK6. Loss of p38 MAPK activation in the mutant cells was associated with defects in growth arrest and increased tumorigenesis. These data indicate that p38 MAPK is regulated by the coordinated and selective actions of three different protein kinases in response to cytokines and exposure to environmental stress.

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Metadata

Authors
Brancho, D., Tanaka, N., Jaeschke, A., Ventura, J.-J., Kelkar, N., Tanaka, Y., Kyuuma, M., Takeshita, T., Flavell, R. A., & Davis, R. J.
Venue
Genes & Development
Published
2003-07-31
Volume
17
Issue
16
Pages
1969-1978
ISSN
  • 0890-9369 (ISSN-L)
  • 1549-5477
OpenAlex
W2167006963
Cited by
490
References
3
Type
posted content
Language
en
Open access
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CoChat. (2026). Citation check: Mechanism of p38 MAP kinase activation in vivo. https://app.cochat.ai/papers/10.1101/gad.1107303
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Brancho, D., Tanaka, N., Jaeschke, A., Ventura, J.-J., Kelkar, N., Tanaka, Y., Kyuuma, M., Takeshita, T., Flavell, R. A., & Davis, R. J. (2003). Mechanism of p38 MAP kinase activation in vivo. Genes & Development. https://doi.org/10.1101/gad.1107303

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