BIOSYNTHESIS OF THE TYPE-I AND TYPE-II TGF-BETA RECEPTORS - IMPLICATIONS FOR COMPLEX-FORMATION

The TGF-beta type I and type II receptors (T beta RI and T beta-RII) a re signaling receptors that form heteromeric cell surface complexes wi th the TGF-beta s as one of the earliest events in the cellular respon se to these multifunctional growth factors. Using TGF-beta-responsive mink lung epithelial cells (Mv1Lu), we have determined the half-lives of the endoplasmic reticulum (ER) and mature forms of these receptors. In metabolically labeled cells, approximately 90% of newly synthesize d type II receptor undergoes modification of N-linked sugars in the Go lgi, with a half-life of 30-35 min; the Golgi-processed form of the re ceptor has a relatively short metabolic half life of 2.5 h. In contras t, only 50% of pulse-labeled type I receptor is converted to the Golgi -processed and therefore endoglycosidase II-resistant form, and the en doglycosidase II-sensitive ER form has a half-life of 2.8-3 h. Additio n of 100 pM TGF-beta 1 causes the Golgi-processed type II receptor to become less stable, with a half-life of 1.7 h, and also destabilizes t he Golgi-processed type I receptor. TGF-beta 1 binding and crosslinkin g experiments on cells treated with tunicamycin for various times conf irm different ER to cell surface processing times for T beta RI and T beta RII. Our results, which suggest that stable complexes between typ e I and II TGF-beta receptors do not form until the proteins reach a p ost-ER compartment (presumably the cell surface), have important impli cations for our understanding of complex formation and receptor regula tion.