PMID- 10347172
OWN - NLM
STAT- MEDLINE
DCOM- 19990701
LR  - 20190613
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 23
DP  - 1999 Jun 4
TI  - Interaction of frizzled related protein (FRP) with Wnt ligands and the frizzled
      receptor suggests alternative mechanisms for FRP inhibition of Wnt signaling.
PG  - 16180-7
AB  - Frizzled related proteins (FRPs) comprise a family of secreted molecules that
      contain an N-terminal cysteine-rich domain (CRD) highly similar to the CRDs of
      the frizzled family of membrane-anchored Wnt receptors. FRPs have been shown to
      interact with Wnt proteins and antagonize Wnt signaling in a Xenopus
      developmental model. We demonstrated that FRP antagonizes the Wnt-induced
      increase in uncomplexed beta-catenin in both transient cotransfection and stable 
      transformation models, where Wnt-induced morphological alterations are inhibited 
      as well. We showed further that FRP inhibits Wnt signaling in a paracrine mode
      using a T-cell factor luciferase reporter to measure Wnt function. Investigation 
      of the mechanisms responsible for FRP inhibition revealed that FRP forms
      complexes with WNT-1 or WNT-2 through its CRD domain. Transfection analysis with 
      FRPs containing different tags revealed that FRP itself forms complexes and that 
      this ability is conferred by its CRD domain. Finally, we demonstrated by
      cotransfection that FRP forms complexes with a prototype frizzled. All of these
      findings are consistent with a model by which FRP inhibits Wnt signaling through 
      interactions with Wnt and/or formation of nonfunctional complexes with the
      frizzled receptor.
FAU - Bafico, A
AU  - Bafico A
AD  - Derald H. Ruttenberg Cancer Center, Mount Sinai School of Medicine, New York, New
      York 10029, USA.
FAU - Gazit, A
AU  - Gazit A
FAU - Pramila, T
AU  - Pramila T
FAU - Finch, P W
AU  - Finch PW
FAU - Yaniv, A
AU  - Yaniv A
FAU - Aaronson, S A
AU  - Aaronson SA
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Glycoproteins)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Ligands)
RN  - 0 (Platelet-Derived Growth Factor)
RN  - 0 (Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (WD repeat containing planar cell polarity effector)
RN  - 0 (WNT1 protein, Xenopus)
RN  - 0 (Wnt Proteins)
RN  - 0 (Wnt1 Protein)
RN  - 0 (Wnt2 Protein)
RN  - 0 (Xenopus Proteins)
RN  - 0 (Zebrafish Proteins)
SB  - IM
MH  - Animals
MH  - *Glycoproteins
MH  - Intracellular Signaling Peptides and Proteins
MH  - Ligands
MH  - Platelet-Derived Growth Factor/metabolism
MH  - Protein Conformation
MH  - Proteins/*metabolism
MH  - Proto-Oncogene Proteins/*metabolism
MH  - *Signal Transduction
MH  - Transfection
MH  - Wnt Proteins
MH  - Wnt1 Protein
MH  - Wnt2 Protein
MH  - Xenopus
MH  - Xenopus Proteins
MH  - *Zebrafish Proteins
EDAT- 1999/05/29 00:00
MHDA- 1999/05/29 00:01
CRDT- 1999/05/29 00:00
PHST- 1999/05/29 00:00 [pubmed]
PHST- 1999/05/29 00:01 [medline]
PHST- 1999/05/29 00:00 [entrez]
AID - 10.1074/jbc.274.23.16180 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Jun 4;274(23):16180-7. doi: 10.1074/jbc.274.23.16180.