Human frizzled 1 interacts with transforming Wnts to transduce a TCF dependent transcriptional response.
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.
Gazit
A
A
Department of Human Microbiology, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel.
Yaniv
A
A
Bafico
A
A
Pramila
T
T
Igarashi
M
M
Kitajewski
J
J
Aaronson
S A
SA
D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D051157:Frizzled Receptors; D006801:Humans; D051821:Lymphoid Enhancer-Binding Factor 1; D008967:Molecular Biology / Q000379:methods; D008969:Molecular Sequence Data; D009154:Mutation; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled; D017981:Receptors, Neurotransmitter / Q000235:genetics* / Q000378:metabolism*; D012680:Sensitivity and Specificity; D017421:Sequence Analysis; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; D051154:Wnt2 Protein; D060508:Wnt3 Protein; D060509:Wnt3A Protein; D060528:Wnt4 Protein; D029961:Zebrafish Proteins
D004268:DNA-Binding Proteins; C489740:FZD1 protein, human; D051157:Frizzled Receptors; C489739:Fzd1 protein, mouse; D051821:Lymphoid Enhancer-Binding Factor 1; D011506:Proteins; D011518:Proto-Oncogene Proteins; D043562:Receptors, G-Protein-Coupled; D017981:Receptors, Neurotransmitter; D014157:Transcription Factors; C495244:WNT2 protein, human; C555510:WNT3A protein, human; C555581:WNT4 protein, human; C085389:WNT5A protein, human; C490674:WNT6 protein, human; C092778:WNT7A protein, human; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; D051154:Wnt2 Protein; D060508:Wnt3 Protein; D060509:Wnt3A Protein; C555511:Wnt3a protein, mouse; D060528:Wnt4 Protein; C555582:Wnt4 protein, mouse; C555583:Wnt4 protein, rat; C490508:Wnt7a protein, mouse; C490507:Wnt7a protein, rat; D029961:Zebrafish Proteins