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cDNA cloning, expression studies and chromosome mapping of human type I serine/threonine kinase receptor ALK7 (ACVR1C)Bondestam J.a,b · Huotari M.-A.a,c · Morén A.e · Ustinov J.a,c · Kaivo-oja N.a,b · Kallio J.a,b · Horelli-Kuitunen N.d · Aaltonen J.a,b · Fujii M.f · Moustakas A.e · ten Dijke P.g · Otonkoski T.a,c · Ritvos O.a,b
aProgram for Developmental and Reproductive Biology, Biomedicum Helsinki; bDepartment of Bacteriology and Immunology, Haartman Institute, University of Helsinki; cTransplantation Laboratory, Haartman Institute and Hospital for Children and Adolescents, University of Helsinki; dDepartment of Clinical Chemistry and Laboratory of Molecular Genetics, Helsinki University Central Hospital, Helsinki (Finland); eLudwig Institute for Cancer Research, Uppsala Branch, Uppsala (Sweden); fDepartment of Biochemistry, The Cancer Institute of the Japanese Foundation for Cancer Research and Research for the Future Program, Japan Society for the Promotion of Science, Tokyo (Japan); gDivision of Cellular Biochemistry, The Netherlands Cancer Institute, Amsterdam (The Netherlands)
Transforming growth factor-β (TGF-β) 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-β 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-βs and activins.
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