Download MendeleyThe TGF beta receptor activation process: an inhibitor- to substrate-binding switch.
Huse, M., Muir, T.W., Xu, L., Chen, Y.G., Kuriyan, J., Massague, J.(2001) Mol Cell 8: 671-682
- PubMed: 11583628
- DOI: https://doi.org/10.1016/s1097-2765(01)00332-x
- Primary Citation of Related Structures:
1IAS - PubMed Abstract:
The type I TGF beta receptor (T beta R-I) is activated by phosphorylation of the GS region, a conserved juxtamembrane segment located just N-terminal to the kinase domain. We have studied the molecular mechanism of receptor activation using a homogeneously tetraphosphorylated form of T beta R-I, prepared using protein semisynthesis. Phosphorylation of the GS region dramatically enhances the specificity of T beta R-I for the critical C-terminal serines of Smad2. In addition, tetraphosphorylated T beta R-I is bound specifically by Smad2 in a phosphorylation-dependent manner and is no longer recognized by the inhibitory protein FKBP12. Thus, phosphorylation activates T beta R-I by switching the GS region from a binding site for an inhibitor into a binding surface for substrate. Our observations suggest that phosphoserine/phosphothreonine-dependent localization is a key feature of the T beta R-I/Smad activation process.
Organizational Affiliation:
Laboratory of Molecular Biophysics, Rockefeller University, New York, NY 10021, USA.
