Molecular cloning and characterization of FRAT2, encoding a positive regulator of the WNT signaling pathway
Abstract
FRAT1 positively regulates the WNT signaling pathway by stabilizing beta-catenin through the association with glycogen synthase kinase-3beta. Here, we have cloned FRAT2 cDNAs, spanning the complete coding sequence, from a human fetal lung cDNA library. FRAT2 encoded 233 amino-acid protein, which showed 77.3% total amino-acid identity with FRAT1. FRAT2 and FRAT1 were more homologous in the acidic domain (96% identity), the proline-rich domain (92% identity), and the GSK-3beta binding domain (100% identity). The FRAT2 gene was mapped to human chromosome 10q24.1. The FRAT2 mRNA of 2.4-kb in size was relatively highly expressed in MKN45 (gastric cancer), HeLa S3 (cervical cancer), and K-562 (chronic myelogenous leukemia). Xenopus axis duplication assay revealed that the wild-type FRAT2 mRNA, but not the mutant FRAT2 mRNA lacking the acidic domain and the proline-rich domain, has the capacity to induce the secondary axis. These results indicate that FRAT2, just like FRAT1, functions as a positive regulator of the WNT signaling pathway. Thus, up-regulation of FRAT2 in human cancer might be implicated in carcinogenesis through activation of the WNT signaling pathway.
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Five activating alterations in Wnt-TGFβ-class (FZD7, FZD6, TCF4, FRAT2 and ARBB2) have been related to Wnt activation in cancer.
“among which five of them (FZD7, FZD6, TCF4, FRAT2 and ARBB2) have been related to Wnt activation in cancer (20-25)”
From Wnt-Pathway Activation in Two Molecular Classes of Hepatocellular Carcinoma and Experimental Modulation by Sorafenib (2012) · cites this paper as [25]
Several genes dysregulated in Wnt-TGFβ-class characterize Wnt-signaling activation in cancer.
“In contrast, several genes dysregulated in Wnt-TGFβ-class characterize Wnt-signaling activation in cancer (20-25) (Fig. 6).”
From Wnt-Pathway Activation in Two Molecular Classes of Hepatocellular Carcinoma and Experimental Modulation by Sorafenib (2012) · cites this paper as [25]
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Wharton, K. A. (2003) · Developmental Biology · doi:10.1006/dbio.2002.0869 · Cited by 315 · see citing works
Lachenmayer, A., Alsinet, C., Savic, R., Cabellos, L., Toffanin, S., Hoshida, Y., Villanueva, A., Minguez, B., Newell, P., Tsai, H.-W., et al. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-11-2322 · Cited by 306 · see citing works
- Authors
- Saitoh, T., Moriwaki, J., Koike, J., Takagi, A., Miwa, T., Shiokawa, K., & Katoh, M.
- Affiliations
- Tokai University (JP)
- National Cancer Center Research Institute (JP)
- The University of Tokyo (JP)
- Corresponding author
- Katoh, Masaru
- Venue
- Biochemical and Biophysical Research Communications
- Publisher
- Elsevier BV
- Published
- 2001-03
- Volume
- 281
- Issue
- 3
- Pages
- 815-820
- ISSN
- 0006-291X (ISSN-L)
- OpenAlex
- W2148893919
- Cited by
- 49
- References
- 0
- Citations by year
- 2026: 1 · 2024: 1 · 2023: 2 · 2022: 5 · 2021: 1 · 2020: 2 · 2019: 1 · 2018: 2 · 2014: 2 · 2013: 1 · 2012: 3
- FWCI
- 1.40
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochemical and Biophysical Research Communications (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- Wnt signaling, β-catenin stabilization, glycogen synthase kinase-3β, acidic domain, proline-rich region, gene mapping, gastric cancer, cervical cancer, chronic myeloid leukemia, carcinogenesis, protein homology
- MeSH terms
- Amino Acid Sequence, Carrier Proteins, Chromosome Mapping, Cloning, Molecular, Humans, Molecular Sequence Data, Neoplasm Proteins, Proto-Oncogene Proteins, RNA, Messenger, Signal Transduction, Sequence Homology, Amino Acid, DNA, Complementary, Gene Expression Profiling, Zebrafish Proteins, Intracellular Signaling Peptides and Proteins, Adaptor Proteins, Signal Transducing, Wnt Proteins
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