Identification and biochemical characterization of a heart-muscle cell transforming growth factor beta-1 receptor.
Binding of human-recombinant transforming growth factor-beta 1 (TGF-beta 1) to the neonatal rat heart-muscle cell (cardiomyocyte) was characterized as a potential element in the cardioprotective pharmacology of this growth factor. The cardiomyocytes were found to express a single class of specific, high-affinity TGF-beta 1 binding sites. Ligand binding to these sites was rapid, saturable, selective, and reversible, characteristics of a receptor-mediated process. Scatchard and iterative non-linear least-squares regression analyses demonstrated that the cardiomyocyte TGF-beta 1 receptor had a Kd < or = 40 pM, a Bmax of approximately 3.4 fmol/10(6) cells, and a density of approximately 2000 binding sites/cell. Binding was selective for TGF-beta 1 as compared with other TGF-beta isoforms (i.e. TGF-beta 2 and -beta 3) and nonrelated cytokines (e.g. acidic fibroblast growth factor). Affinity-binding experiments to probe the molecular nature of the specific binding revealed three types of cardiomyocyte TGF-beta 1 binding proteins, the most prominent of which corresponded to the high-molecular-mass proteoglycan observed in nonmuscle cell types. These data raise the possibility that the known pharmacological effects of TGF-beta 1 on heart muscle may be direct actions via specific receptor-mediated events.
Research Department, Ciba-Geigy Corporation, Summit, NJ 07901.
J
J
Ross
D R
DR
Janero
D
D
Hreniuk
D000345:Affinity Labels; D000818:Animals; D000831:Animals, Newborn; D001665:Binding Sites; D001667:Binding, Competitive; D007457:Iodine Radioisotopes; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000032:analysis* / Q000737:chemistry; D018125:Receptors, Transforming Growth Factor beta; D011994:Recombinant Proteins / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D000345:Affinity Labels; D007457:Iodine Radioisotopes; D011956:Receptors, Cell Surface; D018125:Receptors, Transforming Growth Factor beta; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta