Human frizzled 1 interacts with transforming Wnts to transduce a TCF dependent transcriptional response

Arnona Gazit; Abraham Yaniv; Anna Bafico; Tata Pramila; Makoto Igarashi; Jan Kitajewski; Stuart A. Aaronson

doi:10.1038/sj.onc.1202985

Human frizzled 1 interacts with transforming Wnts to transduce a TCF dependent transcriptional response

Arnona Gazit, Abraham Yaniv, Anna Bafico, Tata Pramila, Makoto Igarashi, Jan Kitajewski, Stuart A. Aaronson

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77 Scopus citations

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 Wnt3a, -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.

Original language	English
Pages (from-to)	5959-5966
Number of pages	8
Journal	Oncogene
Volume	18
Issue number	44
DOIs	https://doi.org/10.1038/sj.onc.1202985
State	Published - 28 Oct 1999

Keywords

Frizzled
Hfz
TCF
Wnt

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title = "Human frizzled 1 interacts with transforming Wnts to transduce a TCF dependent transcriptional response",

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 Wnt3a, -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.",

keywords = "Frizzled, Hfz, TCF, Wnt",

author = "Arnona Gazit and Abraham Yaniv and Anna Bafico and Tata Pramila and Makoto Igarashi and Jan Kitajewski and Aaronson, {Stuart A.}",

note = "Funding Information: This research was supported by NIH R01-CA71672 and a fellowship to Makoto Igarashi from the Leo and Julia Forchheimer Foundation.",

year = "1999",

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doi = "10.1038/sj.onc.1202985",

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T1 - Human frizzled 1 interacts with transforming Wnts to transduce a TCF dependent transcriptional response

AU - Gazit, Arnona

AU - Yaniv, Abraham

AU - Bafico, Anna

AU - Pramila, Tata

AU - Igarashi, Makoto

AU - Kitajewski, Jan

AU - Aaronson, Stuart A.

N1 - Funding Information: This research was supported by NIH R01-CA71672 and a fellowship to Makoto Igarashi from the Leo and Julia Forchheimer Foundation.

PY - 1999/10/28

Y1 - 1999/10/28

N2 - 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 Wnt3a, -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.

AB - 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 Wnt3a, -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.

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ER -

Human frizzled 1 interacts with transforming Wnts to transduce a TCF dependent transcriptional response

Abstract

Keywords

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