Title
Mechanism of p38 MAP kinase activation in vivo
GSBS Program
Biochemistry & Molecular Pharmacology
Publication Date
2003-08-02
UMMS Affiliation
Graduate School of Biomedical Sciences; Program in Molecular Medicine
Document Type
Article
Disciplines
Life Sciences | Medicine and Health Sciences
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.
DOI of Published Version
10.1101/gad.1107303
Source
Genes Dev. 2003 Aug 15;17(16):1969-78. Epub 2003 Jul 31. Link to article on publisher's site
Journal/Book/Conference Title
Genes and development
Related Resources
PubMed ID
12893778
Repository Citation
Brancho DM, Tanaka N, Jaeschke A, Ventura J, Kelkar N, Tanaka Y, Kyuuma M, Takeshita T, Flavell RA, Davis RJ. (2003). Mechanism of p38 MAP kinase activation in vivo. GSBS Student Publications. https://doi.org/10.1101/gad.1107303. Retrieved from https://escholarship.umassmed.edu/gsbs_sp/126