A novel type I receptor serine-threonine kinase predominantly expressed in the adult central nervous system.
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-beta (TGF-beta) 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-beta 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-beta 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.
Rydén
M
M
Laboratory of Molecular Neurobiology, Department of Neuroscience, Karolinska Institute, 171 77 Stockholm, Sweden. carlos@cajal.mbb.ki.se
Imamura
T
T
Jörnvall
H
H
Belluardo
N
N
Neveu
I
I
Trupp
M
M
Okadome
T
T
ten Dijke
P
P
Ibáñez
C F
CF
D029404:Activin Receptors; D000595:Amino Acid Sequence; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D002490:Central Nervous System / Q000502:physiology*; D003001:Cloning, Molecular; D015870:Gene Expression; D008024:Ligands; D008565:Membrane Proteins / Q000737:chemistry; D008969:Molecular Sequence Data; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017978:Receptors, Growth Factor / Q000235:genetics / Q000378:metabolism*; D018125:Receptors, Transforming Growth Factor beta; D015398:Signal Transduction
D008024:Ligands; D008565:Membrane Proteins; D012333:RNA, Messenger; D017978:Receptors, Growth Factor; D018125:Receptors, Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D029404:Activin Receptors