A Novel Type I Receptor Serine-Threonine Kinase Predominantly Expressed in the Adult Central Nervous System

• Published in: The Journal of biological chemistry Vol. 271; no. 48; pp. 30603 - 30609
• Main Authors: Rydén, Mikael, Imamura, Takeshi, Jörnvall, Henrik, Belluardo, Natale, Neveu, Isabelle, Trupp, Miles, Okadome, Toshihide, ten Dijke, Peter, Ibáñez, Carlos F.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 29.11.1996; American Society for Biochemistry and Molecular Biology
• Subjects: Activin Receptors; Amino Acid Sequence; Animals; Cell Membrane - metabolism; Cells, Cultured; Central Nervous System - physiology; Cloning, Molecular; Gene Expression; Ligands; Membrane Proteins - chemistry; Molecular Sequence Data; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - metabolism; Rats; Receptors, Growth Factor - genetics; Receptors, Growth Factor - metabolism; Receptors, Transforming Growth Factor beta; RNA, Messenger - genetics; Signal Transduction
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.271.48.30603

Receptor serine-threonine kinases (RSTK) mediate inhibitory as well as stimulatory signals for growth and differentiation by binding to members of the transforming growth factor-β (TGF-β) superfamily. Over 12 different RSTKs have been isolated so far, displaying wide expression in peripheral tissues and in the nervous system. Here we report the isolation and characterization of a novel type I RSTK termed activin receptor-like kinase-7 (ALK-7) that, unlike other members of this receptor family, is predominantly expressed in the adult central nervous system. The ALK-7 gene encodes a 55-kDa cell-surface protein that exhibits up to 78% amino acid sequence identity in the kinase domain to previously isolated type I receptors for TGF-β and activin. In the extracellular domain, however, ALK-7 is more divergent, displaying comparable similarities with all members of the ALK subfamily. RNase protection and in situ hybridization studies demonstrated a highly specific mRNA distribution restricted to neurons in several regions of the adult rat central nervous system, including cerebellum, hippocampus, and nuclei of the brainstem. Receptor reconstitution and cross-linking experiments indicated that ALK-7 can form complexes with type II RSTKs for TGF-β and activin in a ligand-dependent manner, although direct binding of ALK-7 to ligand in these complexes could not be demonstrated. The specific expression pattern of ALK-7, restricted to the postnatal central nervous system, indicates that this receptor may play an important role in the maturation and maintenance of several neuronal subpopulations.