cDNA cloning, expression studies and chromosome mapping of human type I serine/threonine kinase receptor ALK7 (ACVR1C)

Cytogenet Cell Genet. 2001;95(3-4):157-62. doi: 10.1159/000059339.

Abstract

Transforming growth factor-beta (TGF-beta) superfamily related growth factors signal by binding to transmembrane type I and type II receptor serine/threonine kinases (RSTK), which phosphorylate intracellular Smad transcription factors in response to ligand binding. Here we describe the cloning of the human type I RSTK activin receptor-like kinase 7 (ALK7), an orthologue of the previously identified rat ALK7. Nodal, a TGF-beta member expressed during embryonic development and implicated in developmental events like mesoderm formation and left-right axis specification, was recently shown to signal through ALK7. We found ALK7 mRNA to be most abundantly expressed in human brain, pancreas and colon. A cDNA encoding the open reading frame of ALK7 was obtained from a human brain cDNA library. Furthermore, a P1 artificial chromosome (PAC) clone containing the human ALK7 gene was isolated and fluorescent in situ hybridization (FISH) on metaphase chromosomes identified the gene locus as chromosome 2q24.1-->q3. To test the functionality of the ALK7 signaling, we generated recombinant adenoviruses containing a constitutively active form of ALK7 (Ad-caALK7), which is capable of activating downstream targets in a ligand independent manner. Infection with Ad-caALK7 of MIN6 insulinoma cells, in which ALK7 has previously been shown to be endogenously expressed, led to a marked increase in the phosphorylation of Smad2, a signaling molecule also used by TGF-betas and activins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activin Receptors, Type I / genetics*
  • Activin Receptors, Type I / metabolism
  • Amino Acid Sequence
  • Brain Chemistry / genetics*
  • Chromosome Mapping
  • Cloning, Molecular
  • DNA-Binding Proteins / metabolism
  • Gene Expression
  • Gene Library
  • Humans
  • Insulinoma / genetics
  • Molecular Sequence Data
  • Phosphorylation
  • Protein-Serine-Threonine Kinases / genetics*
  • Protein-Serine-Threonine Kinases / metabolism
  • Signal Transduction / genetics
  • Smad2 Protein
  • Trans-Activators / metabolism
  • Tumor Cells, Cultured

Substances

  • DNA-Binding Proteins
  • SMAD2 protein, human
  • Smad2 Protein
  • Trans-Activators
  • Protein-Serine-Threonine Kinases
  • ACVR1C protein, human
  • Activin Receptors, Type I
  • Acvr1c protein, rat

Associated data

  • GENBANK/AQ129133