The TGF beta receptor activation process: an inhibitor- to substrate-binding switch.
Mol Cell
; 8(3): 671-82, 2001 Sep.
Article
in En
| MEDLINE
| ID: mdl-11583628
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.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Trans-Activators
/
Protein Serine-Threonine Kinases
/
Receptors, Transforming Growth Factor beta
/
Cell Cycle Proteins
/
Activin Receptors, Type I
/
Saccharomyces cerevisiae Proteins
/
DNA-Binding Proteins
Type of study:
Prognostic_studies
Language:
En
Journal:
Mol Cell
Journal subject:
BIOLOGIA MOLECULAR
Year:
2001
Document type:
Article
Affiliation country:
Estados Unidos