Reconstitution and transphosphorylation of TGF-β receptor complexes Journal Article
| Authors: | Ventura, F.; Doody, J.; Liu, F.; Wrana, J. L.; Massagué, J. |
| Article Title: | Reconstitution and transphosphorylation of TGF-β receptor complexes |
| Abstract: | 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. |
| Keywords: | signal transduction; controlled study; nonhuman; protein domain; animal; mammalia; cells, cultured; complex formation; transforming growth factor beta; protein protein interaction; phosphorylation; cloning, molecular; membrane protein; transforming growth factors; immunoprecipitation; receptors, transforming growth factor beta; cytoplasm; spodoptera; protein kinase; ligand binding; yeast cell; cell lysate; mammal cell; cytokine receptor; baculovirus; baculoviridae; membrane receptor; unidentified baculovirus; insecta; Ligand-receptor interaction; human; priority journal; article; support, non-u.s. gov't; support, u.s. gov't, p.h.s.; support, u.s. gov't, non-p.h.s. |
| Journal Title: | EMBO Journal |
| Volume: | 13 |
| Issue: | 23 |
| ISSN: | 0261-4189 |
| Publisher: | Wiley Blackwell |
| Date Published: | 1994-12-01 |
| Start Page: | 5581 |
| End Page: | 5589 |
| Language: | English |
| PROVIDER: | scopus |
| PMCID: | PMC395521 |
| PUBMED: | 7988555 |
| DOI: | 10.1002/j.1460-2075.1994.tb06895.x |
| DOI/URL: | |
| Notes: | Export Date: 14 January 2019 -- Article -- Source: Scopus |
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