cDNA cloning, expression studies and chromosome mapping of human type I serine/threonine kinase receptor ALK7 (ACVR1C).
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.
Bondestam
J
J
Program for Developmental and Reproductive Biology, Biomedicum Helsinki, Helsinki, Finland. jonas.bondestam@helsinki.fi
Huotari
M A
MA
Morén
A
A
Ustinov
J
J
Kaivo-Oja
N
N
Kallio
J
J
Horelli-Kuitunen
N
N
Aaltonen
J
J
Fujii
M
M
Moustakas
A
A
Ten Dijke
P
P
Otonkoski
T
T
Ritvos
O
O
D030201:Activin Receptors, Type I / Q000235:genetics* / Q000378:metabolism; D000595:Amino Acid Sequence; D001923:Brain Chemistry / Q000235:genetics*; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000378:metabolism; D015870:Gene Expression; D015723:Gene Library; D006801:Humans; D007340:Insulinoma / Q000235:genetics; D008969:Molecular Sequence Data; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D051899:Smad2 Protein; D015534:Trans-Activators / Q000378:metabolism; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; C497782:SMAD2 protein, human; D051899:Smad2 Protein; D015534:Trans-Activators; D017346:Protein Serine-Threonine Kinases; C424205:ACVR1C protein, human; D030201:Activin Receptors, Type I; C486044:Acvr1c protein, rat