The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
Signaling by proinflammatory cytokines: oligomerization of TRAF2 and TRAF6 is sufficient for JNK and IKK activation and target gene induction via an amino-terminal effector domain
Open accessAbstract
Interleukin-1 (IL-1) and tumor necrosis factor (TNF-alpha) stimulate transcription factors AP-1 and NF-kappaB through activation of the MAP kinases JNK and p38 and the IkappaB kinase (IKK), respectively. The TNF-alpha and IL-1 signals are transduced through TRAF2 and TRAF6, respectively. Overexpressed TRAF2 or TRAF6 activate JNK, p38, or IKK in the absence of extracellular stimulation. By replacing the carboxy-terminal TRAF domain of TRAF2 and TRAF6 with repeats of the immunophilin FKBP12, we demonstrate that their effector domains are composed of their amino-terminal Zn and RING fingers. Oligomerization of the TRAF2 effector domain results in specific binding to MEKK1, a protein kinase capable of JNK, p38, and IKK activation, and induction of TNF-alpha and IL-1 responsive genes. TNF-alpha also enhances the binding of native TRAF2 to MEKK1 and stimulates the kinase activity of the latter. Thus, TNF-alpha and IL-1 signaling is based on oligomerization of TRAF2 and TRAF6 leading to activation of effector kinases.
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Cites
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Self-citationIndependent Human MAP-Kinase Signal Transduction Pathways Defined by MEK and MKK Isoforms
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Phosphorylation meets ubiquitination: the control of NF-κB activity
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Self-citationSignal transduction by the JNK group of MAP kinases
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TAK1 is a ubiquitin-dependent kinase of MKK and IKK
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Multiple control of interleukin-8 gene expression
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Metadata
- Authors
- Baud, V., Liu, Z.-G., Bennett, B., Suzuki, N., Xia, Y., & Karin, M.
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 1999-05-15
- Volume
- 13
- Issue
- 10
- Pages
- 1297-1308
- ISSN
- 0890-9369 (ISSN-L)
- OpenAlex
- W2116063836
- Cited by
- 464
- References
- 7
- Type
- posted content
- Language
- en
- Open access
- diamond
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- Baud, V., Liu, Z.-G., Bennett, B., Suzuki, N., Xia, Y., & Karin, M. (1999). Signaling by proinflammatory cytokines: oligomerization of TRAF2 and TRAF6 is sufficient for JNK and IKK activation and target gene induction via an amino-terminal effector domain. Genes & Development. https://doi.org/10.1101/gad.13.10.1297
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