PMID- 10391247
OWN - NLM
STAT- MEDLINE
DCOM- 19990721
LR  - 20190613
IS  - 0028-0836 (Print)
IS  - 0028-0836 (Linking)
VI  - 399
IP  - 6738
DP  - 1999 Jun 24
TI  - The TAK1-NLK-MAPK-related pathway antagonizes signalling between beta-catenin and
      transcription factor TCF.
PG  - 798-802
AB  - The Wnt signalling pathway regulates many developmental processes through a
      complex of beta-catenin and the T-cell factor/lymphoid enhancer factor (TCF/LEF) 
      family of high-mobility-group transcription factors. Wnt stabilizes cytosolic
      beta-catenin, which then binds to TCF and activates gene transcription. This
      signalling cascade is conserved in vertebrates, Drosophila and Caenorhabditis
      elegans. In C. elegans, the proteins MOM-4 and LIT-1 regulate Wnt signalling to
      polarize responding cells during embryogenesis. MOM-4 and LIT-1 are homologous to
      TAK1 (a kinase activated by transforming growth factor-beta) mitogen-activated
      protein-kinase-kinase kinase (MAP3K) and MAP kinase (MAPK)-related NEMO-like
      kinase (NLK), respectively, in mammalian cells. These results raise the
      possibility that TAK1 and NLK are also involved in Wnt signalling in mammalian
      cells. Here we show that TAK1 activation stimulates NLK activity and
      downregulates transcriptional activation mediated by beta-catenin and TCF.
      Injection of NLK suppresses the induction of axis duplication by microinjected
      beta-catenin in Xenopus embryos. NLK phosphorylates TCF/LEF factors and inhibits 
      the interaction of the beta-catenin-TCF complex with DNA. Thus, the
      TAK1-NLK-MAPK-like pathway negatively regulates the Wnt signalling pathway.
FAU - Ishitani, T
AU  - Ishitani T
AD  - Department of Molecular Biology, Graduate School of Science, Nagoya University,
      Japan.
FAU - Ninomiya-Tsuji, J
AU  - Ninomiya-Tsuji J
FAU - Nagai, S
AU  - Nagai S
FAU - Nishita, M
AU  - Nishita M
FAU - Meneghini, M
AU  - Meneghini M
FAU - Barker, N
AU  - Barker N
FAU - Waterman, M
AU  - Waterman M
FAU - Bowerman, B
AU  - Bowerman B
FAU - Clevers, H
AU  - Clevers H
FAU - Shibuya, H
AU  - Shibuya H
FAU - Matsumoto, K
AU  - Matsumoto K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
RN  - 0 (CTNNB1 protein, Xenopus)
RN  - 0 (CTNNB1 protein, human)
RN  - 0 (Cytoskeletal Proteins)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (TCF Transcription Factors)
RN  - 0 (TCF7L2 protein, human)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factor 7-Like 2 Protein)
RN  - 0 (Transcription Factors)
RN  - 0 (Xenopus Proteins)
RN  - 0 (beta Catenin)
RN  - 0 (tcf7l2 protein, Xenopus)
RN  - 9007-49-2 (DNA)
RN  - EC 2.7.1.- (NLK protein, human)
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 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.25 (MAP Kinase Kinase Kinases)
RN  - EC 2.7.11.25 (MAP kinase kinase kinase 7)
SB  - IM
MH  - Animals
MH  - COS Cells
MH  - Caenorhabditis elegans
MH  - Calcium-Calmodulin-Dependent Protein Kinases/*metabolism
MH  - Cytoskeletal Proteins/antagonists & inhibitors/genetics/*metabolism
MH  - DNA/metabolism
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins
MH  - *MAP Kinase Kinase Kinases
MH  - *Mitogen-Activated Protein Kinases
MH  - Mutation
MH  - Phosphorylation
MH  - Point Mutation
MH  - Protein Binding
MH  - Protein-Serine-Threonine Kinases/genetics/*metabolism
MH  - *Signal Transduction
MH  - TCF Transcription Factors
MH  - *Trans-Activators
MH  - Transcription Factor 7-Like 2 Protein
MH  - Transcription Factors/antagonists & inhibitors/genetics/*metabolism
MH  - Transfection
MH  - Xenopus
MH  - Xenopus Proteins
MH  - beta Catenin
EDAT- 1999/07/03 10:00
MHDA- 2001/03/23 10:01
CRDT- 1999/07/03 10:00
PHST- 1999/07/03 10:00 [pubmed]
PHST- 2001/03/23 10:01 [medline]
PHST- 1999/07/03 10:00 [entrez]
AID - 10.1038/21674 [doi]
PST - ppublish
SO  - Nature. 1999 Jun 24;399(6738):798-802. doi: 10.1038/21674.