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

Katri M. Koli, Carlos L. Arteaga

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Abstract

Three cell surface transforming growth factor β (TGFβ) receptor (R) proteins regulate the effects of TGFβ isoforms on growth and differentiation. TGFβ-IR and -IIb are transmembrane serine/threonine kinases directly mediating the signaling across the plasma membrane. Both TGFβ 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, TGFβ- IIR was first synthesized as a ~60-kDa endoglycosidase H-sensitive precursor protein, which was converted to a mature ~70-kDa protein. The half-life of metabolically labeled mature TGFβ-IIR was estimated to be 60 min and was further reduced to ~45 min in the presence of exogenous TGFβ1. Minimal internalization of 125I-TGFβ1 at 37 °C was detected suggesting that the rapid turnover was not due to endocytosis and degradation of the ligand- receptor complexes. TGFβ-IR was synthesized as a ~53-kDa precursor protein, which was processed to a mature ~55-kDa receptor protein. The half-life of TGFβ-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 TGFβ-IR and TGFβ-IIR providing a potential additional mechanism for modulation of cellular responses to TGFβs.

Original languageEnglish (US)
Pages (from-to)6423-6427
Number of pages5
JournalJournal of Biological Chemistry
Volume272
Issue number10
DOIs
StatePublished - Mar 7 1997

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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