Biosynthesis of the type I and type II TGF-beta receptors. Implications for complex formation.
The TGF-beta type I and type II receptors (TbetaRI and TbetaRII) are signaling receptors that form heteromeric cell surface complexes with the TGF-betas as one of the earliest events in the cellular response 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 synthesized type II receptor undergoes modification of N-linked sugars in the Golgi, with a half-life of 30-35 min; the Golgi-processed form of the receptor has a relatively short metabolic half-life of 2.5 h. In contrast, only 50% of pulse-labeled type I receptor is converted to the Golgi-processed and therefore endoglycosidase H-resistant form, and the endoglycosidase H-sensitive ER form has a half-life of 2.8-3 h. Addition of 100 pM TGF-beta1 causes the Golgi-processed type II receptor to become less stable, with a half-life of 1.7 h, and also destabilizes the Golgi-processed type I receptor. TGF-beta1 binding and cross-linking experiments on cells treated with tunicamycin for various times confirm different ER to cell surface processing times for TbetaRI and TbetaRII. Our results, which suggest that stable complexes between type I and II TGF-beta receptors do not form until the proteins reach a post-ER compartment (presumably the cell surface), have important implications for our understanding of complex formation and receptor regulation.
Wells
R G
RG
Whitehead Institute, Cambridge, Massachusetts 02142, USA.
Yankelev
H
H
Lin
H Y
HY
Lodish
H F
HF
D030201:Activin Receptors, Type I; D000818:Animals; D002478:Cells, Cultured; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004847:Epithelial Cells; D006056:Golgi Apparatus / Q000378:metabolism; D006207:Half-Life; D006596:Hexosaminidases / Q000378:metabolism; D008168:Lung / Q000166:cytology; D008907:Mink; D011485:Protein Binding; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; 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
D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; 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; D006596:Hexosaminidases