PMID- 10801798
OWN - NLM
STAT- MEDLINE
DCOM- 20000816
LR  - 20231213
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 275
IP  - 27
DP  - 2000 Jul 7
TI  - NESK, a member of the germinal center kinase family that activates the c-Jun 
      N-terminal kinase pathway and is expressed during the late stages of 
      embryogenesis.
PG  - 20533-9
AB  - The c-Jun N-terminal kinase (JNK) signaling pathway plays a crucial role in 
      cellular responses stimulated by stress-inducing agents and proinflammatory 
      cytokines. The group I germinal center kinase family members selectively activate 
      the JNK pathway. In this study, we have isolated a mouse cDNA encoding a protein 
      kinase homologous to Nck-interacting kinase (NIK), a member of the group I 
      germinal center kinase family. This protein kinase is expressed during the late 
      stages of embryogenesis, but not in adult tissues, and thus named NESK (NIK-like 
      embryo-specific kinase). NESK selectively activated the JNK pathway when 
      overexpressed in HEK 293 cells but did not stimulate the p38 kinase or 
      extracellular signal-regulated kinase (ERK) pathways. NESK-induced JNK activation 
      was inhibited by the dominant negative mutants of MEKK1 and MKK4. Tumor necrosis 
      factor (TNF)-alpha or TNF receptor-associated factor 2 (TRAF2) stimulated the 
      NESK activity. Furthermore, the dominant negative NESK mutant inhibited the JNK 
      activation induced by TNF-alpha or TRAF2. These results suggest that NESK, a 
      novel activator of the JNK pathway, functions in coupling TRAF2 to the MEKK1 --> 
      MKK4 --> JNK kinase cascade during the late stages of mammalian embryogenesis.
FAU - Nakano, K
AU  - Nakano K
AD  - Department of Life Science, Faculty of Bioscience and Biotechnology, Tokyo 
      Institute of Technology, Nagatsuta, Midori-ku, Yokohama 226-8501, Japan.
FAU - Yamauchi, J
AU  - Yamauchi J
FAU - Nakagawa, K
AU  - Nakagawa K
FAU - Itoh, H
AU  - Itoh H
FAU - Kitamura, N
AU  - Kitamura N
LA  - eng
SI  - GENBANK/AB035267
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Germinal Center Kinases)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Proteins)
RN  - 0 (TNF Receptor-Associated Factor 2)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.7.1.11 (Nik related kinase)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (TNIK protein, human)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.25 (MAP Kinase Kinase Kinase 1)
RN  - EC 2.7.11.25 (MAP3K1 protein, human)
RN  - EC 2.7.11.25 (Map3k1 protein, mouse)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 4)
RN  - EC 2.7.12.2 (MAP2K4 protein, human)
RN  - EC 2.7.12.2 (Map2k4 protein, mouse)
RN  - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Cell Line
MH  - Cloning, Molecular
MH  - Enzyme Activation
MH  - Gene Expression Regulation, Developmental/*genetics
MH  - Germinal Center Kinases
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins
MH  - JNK Mitogen-Activated Protein Kinases
MH  - *MAP Kinase Kinase 4
MH  - *MAP Kinase Kinase Kinase 1
MH  - Mice
MH  - Mitogen-Activated Protein Kinase Kinases/genetics
MH  - Mitogen-Activated Protein Kinases/*metabolism
MH  - Molecular Sequence Data
MH  - Mutation
MH  - Protein Serine-Threonine Kinases/chemistry/*genetics/*metabolism
MH  - Proteins/metabolism
MH  - Sequence Alignment
MH  - Signal Transduction
MH  - TNF Receptor-Associated Factor 2
MH  - Transfection
MH  - Tumor Necrosis Factor-alpha/pharmacology
MH  - NF-kappaB-Inducing Kinase
EDAT- 2000/05/10 09:00
MHDA- 2000/08/19 11:00
CRDT- 2000/05/10 09:00
PHST- 2000/05/10 09:00 [pubmed]
PHST- 2000/08/19 11:00 [medline]
PHST- 2000/05/10 09:00 [entrez]
AID - S0021-9258(19)79866-4 [pii]
AID - 10.1074/jbc.M001009200 [doi]
PST - ppublish
SO  - J Biol Chem. 2000 Jul 7;275(27):20533-9. doi: 10.1074/jbc.M001009200.