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A Human Suppressor of c-Jun N-terminal Kinase 1 Activation by Tumor Necrosis Factor α
- Source :
- Journal of Biological Chemistry. 272:25816-25823
- Publication Year :
- 1997
- Publisher :
- Elsevier BV, 1997.
-
Abstract
- 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.
- Subjects :
- Molecular Sequence Data
MAP Kinase Kinase Kinase 1
Protein Serine-Threonine Kinases
Biology
Mitogen-activated protein kinase kinase
p38 Mitogen-Activated Protein Kinases
Biochemistry
MAP2K7
Fungal Proteins
Jurkat Cells
Humans
ASK1
Amino Acid Sequence
c-Raf
Molecular Biology
Base Sequence
MAP kinase kinase kinase
Tumor Necrosis Factor-alpha
Cyclin-dependent kinase 4
Cyclin-dependent kinase 2
Intracellular Signaling Peptides and Proteins
JNK Mitogen-Activated Protein Kinases
Gene Products, tax
Cell Biology
Protein-Tyrosine Kinases
Enzyme Activation
Repressor Proteins
Calcium-Calmodulin-Dependent Protein Kinases
Cancer research
biology.protein
Cyclin-dependent kinase 9
Mitogen-Activated Protein Kinases
HeLa Cells
Subjects
Details
- ISSN :
- 00219258
- Volume :
- 272
- Database :
- OpenAIRE
- Journal :
- Journal of Biological Chemistry
- Accession number :
- edsair.doi.dedup.....934b2472681076e1b2b75cbe62ed4c75