PMID- 10581160
OWN - NLM
STAT- MEDLINE
DCOM- 20000106
LR  - 20111117
IS  - 0006-291X (Print)
IS  - 0006-291X (Linking)
VI  - 266
IP  - 1
DP  - 1999 Dec 9
TI  - A GSK3beta phosphorylation site in axin modulates interaction with beta-catenin
      and Tcf-mediated gene expression.
PG  - 28-35
AB  - Upon binding of a Wnt to its receptor, GSK3beta is inhibited through an unknown
      mechanism involving Dishevelled (Dsh), resulting in the dephosphorylation and
      stabilization of beta-catenin, which translocates to the nucleus and interacts
      with Lef/Tcf transcription factors to activate target gene expression. Axin is a 
      scaffold protein which binds beta-catenin and GSK3beta (as well as several other 
      proteins) and thus promotes the phosphorylation of beta-catenin. Here we report
      that Axin is phosphorylated on Ser and Thr residues in several regions in vivo,
      while only one region (amino acids 600-672) is efficiently phosphorylated by
      GSK3beta in vitro. Site-directed mutagenesis, together with in vitro and in vivo 
      phosphorylation assays, demonstrates that Axin residues T609 and S614 are
      physiological GSK3beta targets. Substitutions for one or more of these residues, 
      which lie within a beta-catenin binding site, reduce the ability of Axin to
      modulate Wnt-induced signaling in a Lef/Tcf reporter assay. These amino acid
      substitutions also reduce the binding between Axin and beta-catenin. We propose a
      model in which inhibition of GSK3beta activity upon Wnt signaling leads to the
      dephosphorylation of GSK3beta sites in Axin, resulting in the release of
      beta-catenin from the phosphorylation complex.
CI  - Copyright 1999 Academic Press.
FAU - Jho, E h
AU  - Jho Eh
AD  - Department of Genetics and Development, College of Physicians and Surgeons,
      Columbia University, 701 West 168th Street, New York, New York, 10032, USA.
FAU - Lomvardas, S
AU  - Lomvardas S
FAU - Costantini, F
AU  - Costantini F
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Axin Protein)
RN  - 0 (CTNNB1 protein, human)
RN  - 0 (Cytoskeletal Proteins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Lymphoid Enhancer-Binding Factor 1)
RN  - 0 (Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Repressor Proteins)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
RN  - 0 (Wnt Proteins)
RN  - 0 (Zebrafish Proteins)
RN  - 0 (beta Catenin)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - EC 2.7.11.26 (Glycogen Synthase Kinase 3)
SB  - IM
MH  - Amino Acid Sequence
MH  - Amino Acid Substitution
MH  - Axin Protein
MH  - Binding Sites
MH  - Calcium-Calmodulin-Dependent Protein Kinases/antagonists & inhibitors/*metabolism
MH  - Cell Line
MH  - Cytoskeletal Proteins/*metabolism
MH  - DNA-Binding Proteins/*physiology
MH  - *Gene Expression Regulation
MH  - Glycogen Synthase Kinase 3
MH  - Humans
MH  - Lymphoid Enhancer-Binding Factor 1
MH  - Models, Biological
MH  - Molecular Sequence Data
MH  - Mutagenesis, Site-Directed/genetics
MH  - Phosphorylation
MH  - Precipitin Tests
MH  - Protein Binding
MH  - Proteins/chemistry/genetics/*metabolism
MH  - Proto-Oncogene Proteins/genetics/physiology
MH  - *Repressor Proteins
MH  - Signal Transduction
MH  - *Trans-Activators
MH  - Transcription Factors/*physiology
MH  - Transfection
MH  - Wnt Proteins
MH  - *Zebrafish Proteins
MH  - beta Catenin
EDAT- 1999/12/03 00:00
MHDA- 1999/12/03 00:01
CRDT- 1999/12/03 00:00
PHST- 1999/12/03 00:00 [pubmed]
PHST- 1999/12/03 00:01 [medline]
PHST- 1999/12/03 00:00 [entrez]
AID - 10.1006/bbrc.1999.1760 [doi]
AID - S0006291X99917606 [pii]
PST - ppublish
SO  - Biochem Biophys Res Commun. 1999 Dec 9;266(1):28-35. doi: 10.1006/bbrc.1999.1760.