Processing of the transforming growth factor beta type I and II receptors - Biosynthesis and ligand-induced regulation

Three cell surface transforming growth factor beta (TGF beta) receptor (R) proteins regulate the effects of TGF beta isoforms on growth and differentiation. TGF beta-IR and -IIR are transmembrane serine/threonine kinases directly mediating the signaling across the plasma membrane. Both TGF beta 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, TGF beta-IIR was first synthesized as a similar to 60-kDa endoglycosidase II-sensitive precursor protein, which was converted to a mature similar to 70-kDa protein. The half-life of metabolically labeled mature TGF beta-IIR was estimated to be 60 min and was further reduced to similar to 45 min in the presence of exogenous TGF beta 1. Minimal internalization of I-125-TGF beta 1 at 37 degrees C was detected suggesting that the rapid turnover was not due to endocytosis and degradation of the ligand-receptor complexes. TGF beta-IR was synthesized as a similar to 53-kDa precursor protein, which was processed to a mature similar to 55-kDa receptor protein. The half-life of TGF beta-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 TGF beta-IR and TGF beta-IIR providing a potential additional mechanism for modulation of cellular responses to TGF beta s.