Processing of the transforming growth factor beta type I and II receptors. Biosynthesis and ligand-induced regulation.
Three cell surface transforming growth factor beta (TGFbeta) receptor (R) proteins regulate the effects of TGFbeta isoforms on growth and differentiation. TGFbeta-IR and -IIR are transmembrane serine/threonine kinases directly mediating the signaling across the plasma membrane. Both TGFbeta and its receptors are ubiquitously expressed, hence the fine regulation of the multiplicity of responses most likely involves several levels of control including the regulation of expression, complex formation, and down-regulation of the receptor proteins. In mink lung epithelial cells, TGFbeta-IIR was first synthesized as a approximately 60-kDa endoglycosidase H-sensitive precursor protein, which was converted to a mature approximately 70-kDa protein. The half-life of metabolically labeled mature TGFbeta-IIR was estimated to be 60 min and was further reduced to approximately 45 min in the presence of exogenous TGFbeta1. Minimal internalization of 125I-TGFbeta1 at 37 degrees C was detected suggesting that the rapid turnover was not due to endocytosis and degradation of the ligand-receptor complexes. TGFbeta-IR was synthesized as a approximately 53-kDa precursor protein, which was processed to a mature approximately 55-kDa receptor protein. The half-life of TGFbeta-IR was >12 h. A fraction of tunicamycin-treated type I and II receptors that reach the cell surface was able to associate in the presence of ligand suggesting that heteromeric complexes can form in a post-endoplasmic reticulum compartment before full glycosylation is achieved. These results show differential processing and turnover of TGFbeta-IR and TGFbeta-IIR providing a potential additional mechanism for modulation of cellular responses to TGFbetas.
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D030201:Activin Receptors, Type I; D000345:Affinity Labels; D000818:Animals; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism; D006031:Glycosylation / Q000187:drug effects; D008024:Ligands; D008562:Membrane Glycoproteins / Q000378:metabolism; D008907:Mink; D008970:Molecular Weight; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D014415:Tunicamycin / Q000494:pharmacology
D000345:Affinity Labels; D008024:Ligands; D008562:Membrane Glycoproteins; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D014415:Tunicamycin; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II