Molecular cloning and characterization of FRAT2, encoding a positive regulator of the WNT signaling pathway

Biochem Biophys Res Commun. 2001 Mar 2;281(3):815-20. doi: 10.1006/bbrc.2001.4421.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Amino Acid Sequence
  • Carrier Proteins*
  • Chromosome Mapping
  • Cloning, Molecular
  • DNA, Complementary
  • Gene Expression Profiling
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Molecular Sequence Data
  • Neoplasm Proteins*
  • Proto-Oncogene Proteins / chemistry
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / metabolism*
  • RNA, Messenger / genetics
  • Sequence Homology, Amino Acid
  • Signal Transduction / genetics*
  • Wnt Proteins
  • Zebrafish Proteins*

Substances

  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • DNA, Complementary
  • FRAT1 protein, human
  • FRAT2 protein, human
  • Intracellular Signaling Peptides and Proteins
  • Neoplasm Proteins
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • Wnt Proteins
  • Zebrafish Proteins

Associated data

  • GENBANK/AB045118