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Rho Family GTPases Regulate p38 Mitogen-activated Protein Kinase through the Downstream Mediator Pak1
Abstract
The stress-activated p38 mitogen-activated protein (MAP) kinase defines a subgroup of the mammalian MAP kinases that appear to play a key role in regulating inflammatory responses. Co-expression of constitutively active forms of Rac and Cdc42 leads to activation of p38 while dominant negative Rac and Cdc42 inhibit the ability of interleukin-1 to increase p38 activity. p21-activated kinase 1 (Pak1) is a potential mediator of Rac/Cdc42 signaling, and we observe that Pak1 stimulates p38 activity. A dominant negative Pak1 suppresses both interleukin-1- and Rac/Cdc42-induced p38 activity. Rac and Cdc42 appear to regulate a protein kinase cascade initiated at the level of Pak and leading to activation of p38 and JNK.
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“GTPase-activating proteins (GAPs) such as p50RhoGAP 14 associate with RAC2-GTP to stimulate GTP hydrolysis, resulting in the inactive RAC2-GDP, which again associates with RhoGDI.”
From Dominant activating RAC2 mutation with lymphopenia, immunodeficiency, and cytoskeletal defects (2019) · cites this paper as [14]
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Metadata
- Authors
- Zhang, S., Han, J., Sells, M. A., Chernoff, J., Knaus, U. G., Ulevitch, R. J., & Bokoch, G. M.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1995-10
- Volume
- 270
- Issue
- 41
- Pages
- 23934-23936
- ISSN
- 0021-9258
- Cited by
- 614
- References
- 1
- Language
- en
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