PMID- 10481074
OWN - NLM
STAT- MEDLINE
DCOM- 19991013
LR  - 20190621
IS  - 0014-5793 (Print)
IS  - 0014-5793 (Linking)
VI  - 458
IP  - 2
DP  - 1999 Sep 17
TI  - A GSK3-binding peptide from FRAT1 selectively inhibits the GSK3-catalysed
      phosphorylation of axin and beta-catenin.
PG  - 247-51
AB  - The Axin-dependent phosphorylation of beta-catenin catalysed by glycogen synthase
      kinase-3 (GSK3) is inhibited during embryogenesis. This protects beta-catenin
      against ubiquitin-dependent proteolysis, leading to its accumulation in the
      nucleus, where it controls the expression of genes important for development.
      Frequently rearranged in advanced T-cell lymphomas 1 (FRAT1) is a mammalian
      homologue of a GSK3-binding protein (GBP), which appears to play a key role in
      the correct establishment of the dorsal-ventral axis in Xenopus laevis. Here, we 
      demonstrate that FRATtide (a peptide corresponding to residues 188-226 of FRAT1) 
      binds to GSK3 and prevents GSK3 from interacting with Axin. FRATtide also blocks 
      the GSK3-catalysed phosphorylation of Axin and beta-catenin, suggesting a
      potential mechanism by which GBP could trigger axis formation. In contrast,
      FRATtide does not suppress GSK3 activity towards other substrates, such as
      glycogen synthase and eIF2B, whose phosphorylation is independent of Axin but
      dependent on a 'priming' phosphorylation. This may explain how the essential
      cellular functions of GSK3 can continue, despite the suppression of beta-catenin 
      phosphorylation.
FAU - Thomas, G M
AU  - Thomas GM
AD  - MRC Protein Phosphorylation Unit, MSI/WTB Complex, University of Dundee, UK.
FAU - Frame, S
AU  - Frame S
FAU - Goedert, M
AU  - Goedert M
FAU - Nathke, I
AU  - Nathke I
FAU - Polakis, P
AU  - Polakis P
FAU - Cohen, P
AU  - Cohen P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - FEBS Lett
JT  - FEBS letters
JID - 0155157
RN  - 0 (Axin Protein)
RN  - 0 (CTNNB1 protein, human)
RN  - 0 (Carrier Proteins)
RN  - 0 (Cytoskeletal Proteins)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (FRAT1 protein, human)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Peptide Fragments)
RN  - 0 (Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Repressor Proteins)
RN  - 0 (Trans-Activators)
RN  - 0 (Xenopus Proteins)
RN  - 0 (axin1 protein, Xenopus)
RN  - 0 (beta Catenin)
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  - Amino Acid Sequence
MH  - Animals
MH  - Axin Protein
MH  - Binding, Competitive
MH  - Calcium-Calmodulin-Dependent Protein Kinases/*antagonists &
      inhibitors/*metabolism/physiology
MH  - Carrier Proteins/*metabolism
MH  - Catalysis
MH  - Cell Line
MH  - Cytoskeletal Proteins/*antagonists & inhibitors/metabolism
MH  - Embryonic and Fetal Development/physiology
MH  - Enzyme Inhibitors/*metabolism
MH  - Glycogen Synthase Kinase 3
MH  - Glycogen Synthase Kinases
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins
MH  - Molecular Sequence Data
MH  - *Neoplasm Proteins
MH  - Peptide Fragments/*metabolism
MH  - Phosphorylation
MH  - Proteins/*antagonists & inhibitors/metabolism
MH  - Proto-Oncogene Proteins/*metabolism
MH  - *Repressor Proteins
MH  - Sequence Homology, Amino Acid
MH  - Signal Transduction/physiology
MH  - *Trans-Activators
MH  - Xenopus Proteins
MH  - beta Catenin
EDAT- 1999/09/11 00:00
MHDA- 1999/09/11 00:01
CRDT- 1999/09/11 00:00
PHST- 1999/09/11 00:00 [pubmed]
PHST- 1999/09/11 00:01 [medline]
PHST- 1999/09/11 00:00 [entrez]
AID - S0014-5793(99)01161-8 [pii]
AID - 10.1016/s0014-5793(99)01161-8 [doi]
PST - ppublish
SO  - FEBS Lett. 1999 Sep 17;458(2):247-51. doi: 10.1016/s0014-5793(99)01161-8.