PMID- 10196136
OWN - NLM
STAT- MEDLINE
DCOM- 19990517
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 16
DP  - 1999 Apr 16
TI  - Phosphorylation of axin, a Wnt signal negative regulator, by glycogen synthase
      kinase-3beta regulates its stability.
PG  - 10681-4
AB  - Axin forms a complex with glycogen synthase kinase-3beta (GSK-3beta) and
      beta-catenin and promotes GSK-3beta-dependent phosphorylation of beta-catenin,
      thereby stimulating the degradation of beta-catenin. Because GSK-3beta also
      phosphorylates Axin in the complex, the physiological significance of the
      phosphorylation of Axin was examined. Treatment of COS cells with LiCl, a
      GSK-3beta inhibitor, and okadaic acid, a protein phosphatase inhibitor, decreased
      and increased, respectively, the cellular protein level of Axin. Pulse-chase
      analyses showed that the phosphorylated form of Axin was more stable than the
      unphosphorylated form and that an Axin mutant, in which the possible
      phosphorylation sites for GSK-3beta were mutated, exhibited a shorter half-life
      than wild type Axin. Dvl-1, which was genetically shown to function upstream of
      GSK-3beta, inhibited the phosphorylation of Axin by GSK-3beta in vitro.
      Furthermore, Wnt-3a-containing conditioned medium down-regulated Axin and
      accumulated beta-catenin in L cells and expression of Dvl-1(DeltaPDZ), in which
      the PDZ domain was deleted, suppressed this action of Wnt-3a. These results
      suggest that the phosphorylation of Axin is important for the regulation of its
      stability and that Wnt down-regulates Axin through Dvl.
FAU - Yamamoto, H
AU  - Yamamoto H
AD  - Department of Biochemistry, Hiroshima University School of Medicine, 1-2-3,
      Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
FAU - Kishida, S
AU  - Kishida S
FAU - Kishida, M
AU  - Kishida M
FAU - Ikeda, S
AU  - Ikeda S
FAU - Takada, S
AU  - Takada S
FAU - Kikuchi, A
AU  - Kikuchi A
LA  - eng
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 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Axin Protein)
RN  - 0 (Dishevelled Proteins)
RN  - 0 (Phosphoproteins)
RN  - 0 (Proteins)
RN  - 0 (Repressor Proteins)
RN  - 0 (Wnt Proteins)
RN  - 0 (Wnt3 Protein)
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  - COS Cells
MH  - Calcium-Calmodulin-Dependent Protein Kinases/*metabolism
MH  - Dishevelled Proteins
MH  - Down-Regulation
MH  - Glycogen Synthase Kinase 3
MH  - Glycogen Synthase Kinases
MH  - Phosphoproteins/metabolism
MH  - Phosphorylation
MH  - Proteins/*metabolism
MH  - *Repressor Proteins
MH  - Wnt Proteins
MH  - Wnt3 Protein
EDAT- 1999/04/10 00:00
MHDA- 1999/04/10 00:01
CRDT- 1999/04/10 00:00
PHST- 1999/04/10 00:00 [pubmed]
PHST- 1999/04/10 00:01 [medline]
PHST- 1999/04/10 00:00 [entrez]
AID - 10.1074/jbc.274.16.10681 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Apr 16;274(16):10681-4. doi: 10.1074/jbc.274.16.10681.