PMID- 9371818
OWN - NLM
STAT- MEDLINE
DCOM- 19980108
LR  - 20190501
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 94
IP  - 24
DP  - 1997 Nov 25
TI  - Preferential activation of the p46 isoform of JNK/SAPK in mouse macrophages by 
      TNF alpha.
PG  - 13169-74
AB  - A pleiotropic cytokine, tumor necrosis factor-alpha (TNF alpha), regulates the 
      expression of multiple macrophage gene products and thus contributes a key role 
      in host defense. In this study, we have investigated the specificity and 
      mechanism of activation of members of the c-Jun-NH2-terminal 
      kinase/stress-activated protein kinase (JNK/SAPK) subfamily of mitogen-activated 
      protein kinases (MAPKs) in mouse macrophages in response to stimulation with TNF 
      alpha. Exposure of macrophages to TNF alpha stimulated a preferential increase in 
      catalytic activity of the p46 JNK/SAPK isoform compared with the p54 JNK/SAPK 
      isoform as determined by: (i) separation of p46 and p54 JNK/SAPKs by anion 
      exchange liquid chromatography and (ii) selective immunodepletion of the p46 
      JNK/SAPK from macrophage lysates. To investigate the level of regulation of p46 
      JNK/SAPK activation, we determined the ability of MKK4/SEK1/JNKK, an upstream 
      regulator of JNK/SAPKs, to phosphorylate recombinant kinase-inactive p46 and p54 
      JNK/SAPKs. Endogenous MKK4 was able to transphosphorylate both isoforms. In 
      addition, both the p46 and p54 JNK/SAPK isoforms were phosphorylated on their TPY 
      motif in response to TNF alpha stimulation as reflected by immunoblotting with a 
      phospho-specific antibody that recognizes both kinases. Collectively, these 
      results suggest that the level of control of p46 JNK/SAPK activation is distal 
      not only to MKK4 but also to the p54 JNK/SAPK. Preferential isoform activation 
      within the JNK/SAPK subfamily of MAPKs may be an important mechanism through 
      which TNF alpha regulates macrophage phenotypic heterogeneity and 
      differentiation.
FAU - Chan, E D
AU  - Chan ED
AD  - Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO 
      80206, USA.
FAU - Winston, B W
AU  - Winston BW
FAU - Jarpe, M B
AU  - Jarpe MB
FAU - Wynes, M W
AU  - Wynes MW
FAU - Riches, D W
AU  - Riches DW
LA  - eng
GR  - R01 HL055549/HL/NHLBI NIH HHS/United States
GR  - HL55656/HL/NHLBI NIH HHS/United States
GR  - R01 HL55549/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  - 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 (Tumor Necrosis Factor-alpha)
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)
SB  - IM
MH  - Animals
MH  - Calcium-Calmodulin-Dependent Protein Kinases/*metabolism
MH  - Catalysis
MH  - Cells, Cultured
MH  - Chromatography, Ion Exchange
MH  - Enzyme Activation
MH  - JNK Mitogen-Activated Protein Kinases
MH  - Macrophages/*drug effects/enzymology
MH  - Mice
MH  - *Mitogen-Activated Protein Kinases
MH  - Phosphorylation
MH  - Tumor Necrosis Factor-alpha/*pharmacology
PMC - PMC24281
EDAT- 1997/11/25 00:00
MHDA- 1997/11/25 00:01
PMCR- 1998/05/25
CRDT- 1997/11/25 00:00
PHST- 1997/11/25 00:00 [pubmed]
PHST- 1997/11/25 00:01 [medline]
PHST- 1997/11/25 00:00 [entrez]
PHST- 1998/05/25 00:00 [pmc-release]
AID - 3085 [pii]
AID - 10.1073/pnas.94.24.13169 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1997 Nov 25;94(24):13169-74. doi: 
      10.1073/pnas.94.24.13169.