PMID- 7499190
OWN - NLM
STAT- MEDLINE
DCOM- 19960117
LR  - 20211203
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 270
IP  - 46
DP  - 1995 Nov 17
TI  - Preferential involvement of MEK1 in the tumor necrosis factor-alpha-induced 
      activation of p42mapk/erk2 in mouse macrophages.
PG  - 27391-4
AB  - The pleiotropic cytokine tumor necrosis factor-alpha (TNF alpha) controls the 
      expression of multiple gene products in macrophages and plays an important role 
      in host defense. TNF alpha is recognized by the receptors, CD120a (p55) and 
      CD120b (p75). Ligation of CD120a (p55) by TNF alpha or by anti-receptor agonistic 
      antibodies initiates signal transduction leading to the activation of 
      mitogen-activated protein kinases (MAPKs) (p42mapk/erk2 and p44mapk/erk1). 
      Phosphorylation and activation of MAPK are mediated by MAPK kinase (MEK), a 
      family of Thr/Tyr kinases. In this study, we investigated the preferential 
      involvement of the MEK isoforms MEK1 and MEK2 in the activation of p42mapk/erk2 
      in mouse macrophages stimulated with TNF alpha. Exposure of macrophages to TNF 
      alpha stimulated a time-dependent increase in the activity of MEK1 as measured by 
      an in vitro kinase assay using kinase-inactive p42mapk/erk2 (rMAPKkd) as 
      substrate in the presence of gamma-[32P]ATP. Maximal activation of MEK1 was 
      detected at 10 min poststimulation and coincided with maximal 
      transphosphorylation of Tyr and Thr residues of rMAPKkd. By contrast, there was 
      no evidence of MEK2 activation in macrophages in response to TNF alpha. These 
      data suggest that MEK1 is the preferred substrate for MEK kinase, the upstream 
      kinase implicated in activation of the MAPK pathway in macrophages by TNF alpha.
FAU - Winston, B W
AU  - Winston BW
AD  - Department of Pediatrics, National Jewish Center for Immunology and Respiratory 
      Medicine, Denver, Colorado 80206, USA.
FAU - Remigio, L K
AU  - Remigio LK
FAU - Riches, D W
AU  - Riches DW
LA  - eng
GR  - HL27353/HL/NHLBI NIH HHS/United States
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  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Recombinant Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
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 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 1)
RN  - EC 2.7.12.2 (MAP2K1 protein, human)
RN  - EC 2.7.12.2 (Map2k1 protein, mouse)
RN  - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases)
SB  - IM
MH  - Animals
MH  - Bone Marrow Cells
MH  - Calcium-Calmodulin-Dependent Protein Kinases/isolation & purification/*metabolism
MH  - Cells, Cultured
MH  - Enzyme Activation
MH  - Humans
MH  - Immunoblotting
MH  - Kinetics
MH  - MAP Kinase Kinase 1
MH  - Macrophages/cytology/drug effects/*enzymology
MH  - Mice
MH  - Mice, Inbred C3H
MH  - Mitogen-Activated Protein Kinase 1
MH  - *Mitogen-Activated Protein Kinase Kinases
MH  - Neutrophils/physiology
MH  - Phosphorylation
MH  - Protein Serine-Threonine Kinases/isolation & purification/*metabolism
MH  - Protein-Tyrosine Kinases/isolation & purification/*metabolism
MH  - Recombinant Proteins/isolation & purification/metabolism
MH  - Tumor Necrosis Factor-alpha/*pharmacology
EDAT- 1995/11/17 00:00
MHDA- 1995/11/17 00:01
CRDT- 1995/11/17 00:00
PHST- 1995/11/17 00:00 [pubmed]
PHST- 1995/11/17 00:01 [medline]
PHST- 1995/11/17 00:00 [entrez]
AID - S0021-9258(18)87964-9 [pii]
AID - 10.1074/jbc.270.46.27391 [doi]
PST - ppublish
SO  - J Biol Chem. 1995 Nov 17;270(46):27391-4. doi: 10.1074/jbc.270.46.27391.