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cDNA cloning, expression studies and chromosome mapping of human type I serine/threonine kinase receptor ALK7 (ACVR1C)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwig Institute for Cancer Research.
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2001 (English)In: Cytogenetics and Cell Genetics, ISSN 0301-0171, E-ISSN 1421-9816, Vol. 95, no 3-4, 157-162 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2001. Vol. 95, no 3-4, 157-162 p.
Keyword [en]
Activin Receptors; Type I/*genetics/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/metabolism, Research Support; Non-U.S. Gov't, Signal Transduction/genetics, Trans-Activators/metabolism, Tumor Cells; Cultured
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Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-73642DOI: 10.1159/000059339PubMedID: 12063393OAI: oai:DiVA.org:uu-73642DiVA: diva2:101552
Available from: 2005-06-13 Created: 2005-06-13 Last updated: 2013-10-30Bibliographically approved

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Morén, AnitaMoustakas, Aristidisten Dijke, Peter

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