PMID- 10428961
OWN - NLM
STAT- MEDLINE
DCOM- 19990916
LR  - 20190613
IS  - 0261-4189 (Print)
IS  - 0261-4189 (Linking)
VI  - 18
IP  - 15
DP  - 1999 Aug 2
TI  - Axin and Frat1 interact with dvl and GSK, bridging Dvl to GSK in Wnt-mediated
      regulation of LEF-1.
PG  - 4233-40
AB  - Wnt proteins transduce their signals through dishevelled (Dvl) proteins to
      inhibit glycogen synthase kinase 3beta (GSK), leading to the accumulation of
      cytosolic beta-catenin and activation of TCF/LEF-1 transcription factors. To
      understand the mechanism by which Dvl acts through GSK to regulate LEF-1, we
      investigated the roles of Axin and Frat1 in Wnt-mediated activation of LEF-1 in
      mammalian cells. We found that Dvl interacts with Axin and with Frat1, both of
      which interact with GSK. Similarly, the Frat1 homolog GBP binds Xenopus
      Dishevelled in an interaction that requires GSK. We also found that Dvl, Axin and
      GSK can form a ternary complex bridged by Axin, and that Frat1 can be recruited
      into this complex probably by Dvl. The observation that the Dvl-binding domain of
      either Frat1 or Axin was able to inhibit Wnt-1-induced LEF-1 activation suggests 
      that the interactions between Dvl and Axin and between Dvl and Frat may be
      important for this signaling pathway. Furthermore, Wnt-1 appeared to promote the 
      disintegration of the Frat1-Dvl-GSK-Axin complex, resulting in the dissociation
      of GSK from Axin. Thus, formation of the quaternary complex may be an important
      step in Wnt signaling, by which Dvl recruits Frat1, leading to Frat1-mediated
      dissociation of GSK from Axin.
FAU - Li, L
AU  - Li L
AD  - Department of Pharmacology and Physiology, University of Rochester, NY 14642,
      USA.
FAU - Yuan, H
AU  - Yuan H
FAU - Weaver, C D
AU  - Weaver CD
FAU - Mao, J
AU  - Mao J
FAU - Farr, G H 3rd
AU  - Farr GH 3rd
FAU - Sussman, D J
AU  - Sussman DJ
FAU - Jonkers, J
AU  - Jonkers J
FAU - Kimelman, D
AU  - Kimelman D
FAU - Wu, D
AU  - Wu D
LA  - eng
GR  - GM53162/GM/NIGMS NIH HHS/United States
GR  - GM54167/GM/NIGMS NIH HHS/United States
GR  - HD27262/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - EMBO J
JT  - The EMBO journal
JID - 8208664
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Axin Protein)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (DVL1 protein, Xenopus)
RN  - 0 (Dishevelled Proteins)
RN  - 0 (Lymphoid Enhancer-Binding Factor 1)
RN  - 0 (Phosphoproteins)
RN  - 0 (Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Repressor Proteins)
RN  - 0 (Transcription Factors)
RN  - 0 (WNT1 protein, Xenopus)
RN  - 0 (Wnt Proteins)
RN  - 0 (Wnt1 Protein)
RN  - 0 (Xenopus Proteins)
RN  - 0 (Zebrafish Proteins)
RN  - 0 (axin1 protein, Xenopus)
RN  - EC 2.7.11.- (Glycogen Synthase Kinases)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - EC 2.7.11.26 (Glycogen Synthase Kinase 3)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing
MH  - Animals
MH  - Axin Protein
MH  - Calcium-Calmodulin-Dependent Protein Kinases/*metabolism
MH  - DNA-Binding Proteins/*metabolism
MH  - Dishevelled Proteins
MH  - Glycogen Synthase Kinase 3
MH  - Glycogen Synthase Kinases
MH  - Lymphoid Enhancer-Binding Factor 1
MH  - Phosphoproteins/*metabolism
MH  - Protein Binding
MH  - Protein Conformation
MH  - Proteins/*metabolism
MH  - Proto-Oncogene Proteins/*metabolism
MH  - *Repressor Proteins
MH  - Signal Transduction
MH  - Transcription Factors/*metabolism
MH  - Wnt Proteins
MH  - Wnt1 Protein
MH  - Xenopus
MH  - Xenopus Proteins
MH  - *Zebrafish Proteins
PMC - PMC1171499
EDAT- 1999/08/03 10:00
MHDA- 2001/03/28 10:01
CRDT- 1999/08/03 10:00
PHST- 1999/08/03 10:00 [pubmed]
PHST- 2001/03/28 10:01 [medline]
PHST- 1999/08/03 10:00 [entrez]
AID - 10.1093/emboj/18.15.4233 [doi]
PST - ppublish
SO  - EMBO J. 1999 Aug 2;18(15):4233-40. doi: 10.1093/emboj/18.15.4233.