PMID- 9275204
OWN - NLM
STAT- MEDLINE
DCOM- 19971001
LR  - 20230413
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 94
IP  - 18
DP  - 1997 Sep 2
TI  - Tumor necrosis factor (TNF)-mediated kinase cascades: bifurcation of nuclear 
      factor-kappaB and c-jun N-terminal kinase (JNK/SAPK) pathways at TNF 
      receptor-associated factor 2.
PG  - 9792-6
AB  - TNF-induced activation of the transcription factor NF-kappaB and the c-jun 
      N-terminal kinase (JNK/SAPK) requires TNF receptor-associated factor 2 (TRAF2). 
      The NF-kappaB-inducing kinase (NIK) associates with TRAF2 and mediates TNF 
      activation of NF-kappaB. Herein we show that NIK interacts with additional 
      members of the TRAF family and that this interaction requires the conserved "WKI" 
      motif within the TRAF domain. We also investigated the role of NIK in JNK 
      activation by TNF. Whereas overexpression of NIK potently induced NF-kappaB 
      activation, it failed to stimulate JNK activation. A kinase-inactive mutant of 
      NIK was a dominant negative inhibitor of NF-kappaB activation but did not 
      suppress TNF- or TRAF2-induced JNK activation. Thus, TRAF2 is the bifurcation 
      point of two kinase cascades leading to activation of NF-kappaB and JNK, 
      respectively.
FAU - Song, H Y
AU  - Song HY
AD  - Tularik, Two Corporate Drive, South San Francisco, CA 94080, USA.
FAU - Regnier, C H
AU  - Regnier CH
FAU - Kirschning, C J
AU  - Kirschning CJ
FAU - Goeddel, D V
AU  - Goeddel DV
FAU - Rothe, M
AU  - Rothe M
LA  - eng
PT  - Journal Article
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 (NF-kappa B)
RN  - 0 (Proteins)
RN  - 0 (TNF Receptor-Associated Factor 2)
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  - Calcium-Calmodulin-Dependent Protein Kinases/*metabolism
MH  - Cell Line
MH  - Humans
MH  - JNK Mitogen-Activated Protein Kinases
MH  - *Mitogen-Activated Protein Kinases
MH  - Mutation
MH  - NF-kappa B/*metabolism
MH  - Proteins/genetics/*metabolism
MH  - Signal Transduction/*drug effects
MH  - TNF Receptor-Associated Factor 2
MH  - Tumor Necrosis Factor-alpha/metabolism/*pharmacology
PMC - PMC23270
EDAT- 1997/09/02 00:00
MHDA- 1997/09/02 00:01
PMCR- 1998/03/02
CRDT- 1997/09/02 00:00
PHST- 1997/09/02 00:00 [pubmed]
PHST- 1997/09/02 00:01 [medline]
PHST- 1997/09/02 00:00 [entrez]
PHST- 1998/03/02 00:00 [pmc-release]
AID - 2176 [pii]
AID - 10.1073/pnas.94.18.9792 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1997 Sep 2;94(18):9792-6. doi: 10.1073/pnas.94.18.9792.