Open AccessRequirement of mitogen-activated protein kinase kinase 3 (MKK3) for tumor necrosis factor-induced cytokine expression
Author(s) -
Mark Allen Wysk,
Derek D. Yang,
Hongtao Lu,
Richard A. Flavell,
Roger J. Davis
Publication year - 1999
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.96.7.3763
Subject(s) - ask1 , map kinase kinase kinase , map2k7 , mitogen activated protein kinase kinase , microbiology and biotechnology , p38 mitogen activated protein kinases , cyclin dependent kinase 9 , mitogen activated protein kinase , mapk7 , mapk14 , cancer research , protein kinase r , c raf , protein kinase a , biology , cyclin dependent kinase 2 , kinase
The p38 mitogen-activated protein kinase is activated by treatment of cells with cytokines and by exposure to environmental stress. The effects of these stimuli on p38 MAP kinase are mediated by the MAP kinase kinases (MKKs) MKK3, MKK4, and MKK6. We have examined the function of the p38 MAP kinase signaling pathway by investigating the effect of targeted disruption of theMkk3 gene. Here we report thatMkk3 gene disruption caused a selective defect in the response of fibroblasts to the proinflammatory cytokine tumor necrosis factor, including reduced p38 MAP kinase activation and cytokine expression. These data demonstrate that the MKK3 protein kinase is a critical component of a tumor necrosis factor-stimulated signaling pathway that causes increased expression of inflammatory cytokines.