Reconstitution and transphosphorylation of TGF-β receptor complexes

Francesc Ventura, Jacqueline Doody, Fang Liu, Jeffrey L. Wrana, Joan Massagué

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79 Scopus citations


Transforming growth factor-β (TGF-β) signals by contacting two distantly related transmembrane serine/threonine kinases called receptors I (TβR-I) and II (TβR-II). TGF-β binds to TβR-II, which is a constitutively active kinase and this complex recruits TβR-I, causing its phosphorylation and signal propagation to downstream substrates. The biochemical properties of this interaction were analyzed with reconstituted receptor systems. TβR-I and TβR-II baculovirally expressed at high levels in insect cells have the ligand binding properties of receptors expressed in mammalian cells, and form a complex in which TβR-I phosphorylation is dependent on the kinase activity of TβR-II. Furthermore, TβR-I and TβR-II can form a complex in vitro, and their cytoplasmic domains can specifically interact in a yeast two-hybrid system. In vitro complex formation with catalytically active TβR-II is necessary and sufficient for TβR-I phosphorylation, which within this complex does not require the catalytic activity of TβR-I, thus mimicking TβR-I phosphorylation in intact cells. In addition, TβR-I phosphorylated in vitro remains associated with TβR-II. These results suggest that TβR-I and TβR-II have affinity for each other, however, the ligand is required for stable complex formation under physiological conditions. Once formed, this complex is sufficient for TβR-I phosphorylation by TβR-II.

Original languageEnglish (US)
Pages (from-to)5581-5589
Number of pages9
JournalEMBO Journal
Issue number23
StatePublished - Dec 1 1994
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)


  • Ligand-receptor interaction
  • Signal transduction
  • Transforming growth factors


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