PMID- 10097111
OWN - NLM
STAT- MEDLINE
DCOM- 19990512
LR  - 20211203
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 96
IP  - 7
DP  - 1999 Mar 30
TI  - Requirement of mitogen-activated protein kinase kinase 3 (MKK3) for tumor
      necrosis factor-induced cytokine expression.
PG  - 3763-8
AB  - 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 the Mkk3 gene. Here we report 
      that Mkk3 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.
FAU - Wysk, M
AU  - Wysk M
AD  - Howard Hughes Medical Institute and Program in Molecular Medicine, Department of 
      Biochemistry and Molecular Biology, University of Massachusetts Medical School,
      Worcester, MA 01605, USA.
FAU - Yang, D D
AU  - Yang DD
FAU - Lu, H T
AU  - Lu HT
FAU - Flavell, R A
AU  - Flavell RA
FAU - Davis, R J
AU  - Davis RJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Cytokines)
RN  - 0 (Interleukin-1)
RN  - 0 (Interleukin-6)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 506T60A25R (Sorbitol)
RN  - EC 2.7.1.- (MAP-kinase-activated kinase 3)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Calcium-Calmodulin-Dependent Protein Kinases/metabolism
MH  - Cells, Cultured
MH  - Cytokines/*genetics
MH  - Fibroblasts/cytology/physiology
MH  - *Gene Expression Regulation/drug effects/radiation effects
MH  - Interleukin-1/genetics
MH  - Interleukin-6/genetics
MH  - Intracellular Signaling Peptides and Proteins
MH  - JNK Mitogen-Activated Protein Kinases
MH  - Mice
MH  - Mice, Knockout
MH  - *Mitogen-Activated Protein Kinases
MH  - Molecular Sequence Data
MH  - Protein Serine-Threonine Kinases/deficiency/*genetics/*metabolism
MH  - Restriction Mapping
MH  - Sorbitol/pharmacology
MH  - Tumor Necrosis Factor-alpha/*physiology
MH  - Ultraviolet Rays
MH  - p38 Mitogen-Activated Protein Kinases
PMC - PMC22368
EDAT- 1999/03/31 00:00
MHDA- 1999/03/31 00:01
CRDT- 1999/03/31 00:00
PHST- 1999/03/31 00:00 [pubmed]
PHST- 1999/03/31 00:01 [medline]
PHST- 1999/03/31 00:00 [entrez]
AID - 10.1073/pnas.96.7.3763 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):3763-8. doi: 10.1073/pnas.96.7.3763.