PMID- 9325311
OWN - NLM
STAT- MEDLINE
DCOM- 19971113
LR  - 20211203
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 272
IP  - 41
DP  - 1997 Oct 10
TI  - A human suppressor of c-Jun N-terminal kinase 1 activation by tumor necrosis 
      factor alpha.
PG  - 25816-23
AB  - Tumor necrosis factor alpha (TNFalpha) has pleiotropic effects on cellular 
      metabolism. One of the signaling paths from the TNFalpha receptor induces a 
      stress-activated protein kinase cascade. Components within this TNFalpha kinase 
      cascade include mitogen-activated protein kinase/extracellular signal-regulated 
      kinase kinase kinase 1 (MEKK1) and stress-activated protein kinase/extracellular 
      signal-regulated kinase kinase (SEK), which regulate the activity of c-Jun 
      N-terminal kinase 1 (JNK1). Currently, molecules upstream of MEKK1 that link 
      TNFalpha receptor to downstream kinases are not well understood. Besides 
      TNFalpha, many other stimuli including several oncoproteins can activate JNK1. In 
      most cases, the signaling cascade(s) leading from oncoproteins to JNK1 is poorly 
      elucidated. We report here that the human T-cell lymphotrophic virus, type I 
      (HTLV-I) oncoprotein, Tax, can activate JNK1. We isolated a novel human cell 
      factor, G-protein pathway suppressor 2 (GPS2), by its ability to bind the HTLV-I 
      oncoprotein, and we show that this factor can potently suppress Tax activation of 
      JNK1. In trying to understand the mechanism of GPS2 activity, we found that it 
      also suppressed TNFalpha activation of JNK1 but not TNFalpha activation of p38 
      kinase nor phorbol activation of extracellular signal-regulated kinase 2. Because 
      GPS2 has minimal effect on MEKK1- or SEK-regulated JNK1 activity, it could act at 
      a point between the TNFalpha receptor and MEKK1 in the initial step(s) of this 
      kinase cascade. Alternatively, it is not excluded that GPS2 could work in a 
      parallel pathway that leads from TNFalpha to JNK1. GPS2 represents a new molecule 
      that could contribute important insights toward how cytokine- and 
      oncoprotein-mediated signal transduction might converge.
FAU - Jin, D Y
AU  - Jin DY
AD  - Molecular Virology Section, Laboratory of Molecular Microbiology, NIAID, National 
      Institutes of Health, Bethesda, Maryland 20892-0460, USA.
FAU - Teramoto, H
AU  - Teramoto H
FAU - Giam, C Z
AU  - Giam CZ
FAU - Chun, R F
AU  - Chun RF
FAU - Gutkind, J S
AU  - Gutkind JS
FAU - Jeang, K T
AU  - Jeang KT
LA  - eng
SI  - GENBANK/U28963
PT  - Journal Article
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Fungal Proteins)
RN  - 0 (GPS2 protein, human)
RN  - 0 (Gene Products, tax)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Repressor 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 (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)
RN  - EC 2.7.11.25 (MAP Kinase Kinase Kinase 1)
RN  - EC 2.7.11.25 (MAP3K1 protein, human)
SB  - IM
MH  - Amino Acid Sequence
MH  - Base Sequence
MH  - Calcium-Calmodulin-Dependent Protein Kinases/*antagonists & inhibitors/metabolism
MH  - Enzyme Activation
MH  - Fungal Proteins/metabolism
MH  - Gene Products, tax/metabolism/*pharmacology
MH  - HeLa Cells
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins
MH  - JNK Mitogen-Activated Protein Kinases
MH  - Jurkat Cells
MH  - *MAP Kinase Kinase Kinase 1
MH  - *Mitogen-Activated Protein Kinases
MH  - Molecular Sequence Data
MH  - Protein Serine-Threonine Kinases/metabolism
MH  - Protein-Tyrosine Kinases/metabolism
MH  - *Repressor Proteins
MH  - Tumor Necrosis Factor-alpha/metabolism/*pharmacology
MH  - p38 Mitogen-Activated Protein Kinases
EDAT- 1997/11/05 00:00
MHDA- 1997/11/05 00:01
CRDT- 1997/11/05 00:00
PHST- 1997/11/05 00:00 [pubmed]
PHST- 1997/11/05 00:01 [medline]
PHST- 1997/11/05 00:00 [entrez]
AID - S0021-9258(18)60180-2 [pii]
AID - 10.1074/jbc.272.41.25816 [doi]
PST - ppublish
SO  - J Biol Chem. 1997 Oct 10;272(41):25816-23. doi: 10.1074/jbc.272.41.25816.