Habrec1, a novel serine/threonine kinase TGF-beta type I-like receptor, has a specific cellular expression suggesting function in the developing organism and adult brain.
Members of the TGF-beta superfamily signal through a dual receptor system consisting of a type II receptor protein kinase that binds the ligand, after which this complex associates with a type I receptor to mediate intracellular signaling. In mammals, six type I and five type II receptors mediating responses to different TGF-beta family members have been identified to date. Using primers from conserved regions of the protein kinase domain of the serine/threonine kinase receptors in a low-stringency polymerase chain reaction-based screening procedure, and deselecting known receptors with colony hybridization, we now report cloning a novel receptor member. The novel receptor was found in a cDNA library prepared from the habenular nucleus area and was designated Habrec1. Although only a partial sequence is available, it fits the criteria for a TGF-beta type I serine/threonine kinase receptor. In situ hybridization of Habrec1 reveals mRNA expression in several distinct areas of the developing central nervous system, including cortex cerebri, cerebellum, hippocampus, striatum, and thalamic nuclei. Expression is also seen in the anterior pituitary. In the periphery, strong expression prenatally includes brown fat, the gastrointestinal tract, liver, pancreas, thymus, and nasal cavity epithelium. In the adult brain Habrec1 mRNA is prominently found in cerebellum, cortex cerebri, and striatum, but at lower levels in several additional areas. We conclude that Habrec1 is a member of the TGF-beta type I receptor family with expression patterns in the developing animal, suggesting specific functions in and outside the nervous system, and in the adult CNS, suggesting roles in both cortical and subcortical brain circuitry.
Lorentzon
M
M
Department of Neuroscience, Karolinska Institute, Stockholm, Sweden.
Hoffer
B
B
Ebendal
T
T
Olson
L
L
Tomac
A
A
D002001:Adipose Tissue, Brown / Q000737:chemistry / Q000201:enzymology; D000818:Animals; D001921:Brain / Q000196:embryology / Q000201:enzymology / Q000254:growth & development; D001923:Brain Chemistry / Q000502:physiology*; D002531:Cerebellum / Q000737:chemistry / Q000201:enzymology; D002540:Cerebral Cortex / Q000737:chemistry / Q000201:enzymology; D018076:DNA, Complementary / Q000235:genetics; D004064:Digestive System / Q000737:chemistry / Q000201:enzymology; D029721:Drosophila Proteins; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D019262:Habenula / Q000737:chemistry / Q000201:enzymology; D006624:Hippocampus / Q000737:chemistry / Q000201:enzymology; D017403:In Situ Hybridization; D007457:Iodine Radioisotopes; D008099:Liver / Q000737:chemistry / Q000201:enzymology; D008297:Male; D008969:Molecular Sequence Data; D017072:Neostriatum / Q000737:chemistry / Q000201:enzymology; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000187:drug effects / Q000235:genetics; D051096:Proto-Oncogene Proteins c-ret; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020794:Receptor Protein-Tyrosine Kinases / Q000187:drug effects / Q000235:genetics; D017978:Receptors, Growth Factor / Q000235:genetics*; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid
D018076:DNA, Complementary; D029721:Drosophila Proteins; C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; C102422:Habrec1 receptor, rat; D007457:Iodine Radioisotopes; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D017978:Receptors, Growth Factor; D018125:Receptors, Transforming Growth Factor beta; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila; D017346:Protein Serine-Threonine Kinases