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PMID:10557084

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Citation

Gazit, A, Yaniv, A, Bafico, A, Pramila, T, Igarashi, M, Kitajewski, J and Aaronson, SA (1999) Human frizzled 1 interacts with transforming Wnts to transduce a TCF dependent transcriptional response. Oncogene 18:5959-66

Abstract

The human homologue of fz1 (Hfz1) was cloned from a cDNA library. Hfz1 was shown to couple to Wnt signal transduction pathways by its ability to enhance Wnt induced TCF dependent transcription in both autocrine and paracrine modes. Enhanced TCF dependent signaling was dose dependent with respect to both Wnt-3A and Hfz1. Moreover, Hfz1 deletion mutants with truncated carboxy termini showed markedly reduced capacity to enhance Wnt signal transduction. Specificity was demonstrated with respect to signal transduction by different Wnts. While Wnt-3a, -3, -1 and to a lesser extent Wnt-2 cooperated with Hfz1 in the paracrine assay for TCF dependent signaling, neither Wnt-4, -5a, -5b, -6, -7a nor -7b did so, despite similar levels of expression. However, coimmunoprecipitation of Hfz1 with both Wnt-3a and Wnt-5a indicated that TCF dependent signaling in response to Wnts is not determined solely by their ability to bind the receptor. All of these findings provide strong evidence that Hfz1 is a functional partner for certain Wnts in inducing TCF dependent transcription.

Links

PubMed Online version:10.1038/sj.onc.1202985

Keywords

Cell Line; Cell Transformation, Neoplastic; Cloning, Molecular; DNA-Binding Proteins/genetics; DNA-Binding Proteins/metabolism; Frizzled Receptors; Humans; Lymphoid Enhancer-Binding Factor 1; Molecular Biology/methods; Molecular Sequence Data; Mutation; Proteins/genetics; Proteins/metabolism; Proto-Oncogene Proteins/genetics; Proto-Oncogene Proteins/metabolism; Receptors, G-Protein-Coupled; Receptors, Neurotransmitter/genetics; Receptors, Neurotransmitter/metabolism; Sensitivity and Specificity; Sequence Analysis; Signal Transduction; Transcription Factors/genetics; Transcription Factors/metabolism; Transcription, Genetic; Transfection; Wnt Proteins; Wnt2 Protein; Wnt3 Protein; Wnt3A Protein; Wnt4 Protein; Zebrafish Proteins

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:WNT1

enables

GO:0048018: receptor ligand activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:WNT2

enables

GO:0048018: receptor ligand activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:WNT3A

enables

GO:0048018: receptor ligand activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:WNT3

enables

GO:0048018: receptor ligand activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:FZD1

part_of

GO:1990909: Wnt signalosome

ECO:0000305: curator inference used in manual assertion

GO:0042813
GO:0060070

C

Seeded From UniProt

complete

HUMAN:FZD1

enables

GO:0042813: Wnt-activated receptor activity

ECO:0000314: direct assay evidence used in manual assertion

F

  • has_input:(UniProtKB:P56704)|has_input:(UniProtKB:P56703)|has_input:(UniProtKB:P04628)|has_input:(UniProtKB:P09544)

Seeded From UniProt

complete

HUMAN:FZD1

involved_in

GO:0007267: cell-cell signaling

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:FZD1

enables

GO:0017147: Wnt-protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P22725

F

Seeded From UniProt

complete

HUMAN:FZD1

involved_in

GO:0051091: positive regulation of DNA-binding transcription factor activity

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:FZD1

involved_in

GO:0035425: autocrine signaling

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:FZD1

enables

GO:0017147: Wnt-protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P56703

F

Seeded From UniProt

complete

HUMAN:FZD1

enables

GO:0017147: Wnt-protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P09544

F

Seeded From UniProt

complete

HUMAN:FZD1

involved_in

GO:0060070: canonical Wnt signaling pathway

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:WNT3

enables

GO:0048018: receptor ligand activity

ECO:0000314: direct assay evidence used in manual assertion

F

part_of:(GO:0016055)

Seeded From UniProt

complete

HUMAN:WNT3

part_of

GO:1990909: Wnt signalosome

ECO:0000305: curator inference used in manual assertion

GO:0048018
GO:0060070

C

Seeded From UniProt

complete

HUMAN:WNT3

involved_in

GO:0060070: canonical Wnt signaling pathway

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:WNT3

enables

GO:0005109: frizzled binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9UP38

F

Seeded From UniProt

complete

HUMAN:WNT2

enables

GO:0005109: frizzled binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9UP38

F

Seeded From UniProt

complete

HUMAN:WNT2

involved_in

GO:0060070: canonical Wnt signaling pathway

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:WNT2

involved_in

GO:0007267: cell-cell signaling

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:WNT2

enables

GO:0005125: cytokine activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:WNT2

involved_in

GO:0051091: positive regulation of DNA-binding transcription factor activity

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:WNT2

enables

GO:0048018: receptor ligand activity

ECO:0000314: direct assay evidence used in manual assertion

F

part_of:(GO:0016055)

Seeded From UniProt

complete

HUMAN:WNT2

part_of

GO:1990909: Wnt signalosome

ECO:0000305: curator inference used in manual assertion

GO:0048018
GO:0060070

C

Seeded From UniProt

complete

MOUSE:WNT5A

enables

GO:0005109: frizzled binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9UP38

F

Seeded From UniProt

complete

MOUSE:WNT1

enables

GO:0005125: cytokine activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:WNT1

involved_in

GO:0007267: cell-cell signaling

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:WNT1

enables

GO:0048018: receptor ligand activity

ECO:0000314: direct assay evidence used in manual assertion

F

part_of:(GO:0016055)

Seeded From UniProt

complete

MOUSE:WNT1

part_of

GO:1990909: Wnt signalosome

ECO:0000305: curator inference used in manual assertion

GO:0048018

C

Seeded From UniProt

complete

MOUSE:WNT3A

involved_in

GO:0060070: canonical Wnt signaling pathway

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:WNT3A

enables

GO:0048018: receptor ligand activity

ECO:0000314: direct assay evidence used in manual assertion

F

part_of:(GO:0016055)

Seeded From UniProt

complete

MOUSE:WNT3A

part_of

GO:1990909: Wnt signalosome

ECO:0000305: curator inference used in manual assertion

GO:0048018
GO:0060070

C

Seeded From UniProt

complete


See also

References

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