Abstract
The FK506-binding protein, FKBP12, is a putative target of type I receptors for transforming growth factor-beta (TbetaR-I). As the FK506 motif that competes with TbetaR-I for FKBP12 resembles an invariant Leu-Pro dipeptide in TbetaR-I, we replaced Leu193 and Pro194 with Ala, along with mutations across the Gly/Ser box. L193A, P194A, and L193A/P194A do not alter TbetaR-I function; T204D partially activates, independent of ligand; L193A/P194A/T204D was an even more potent constitutive mutation. Association with FKBP12 in a yeast two-hybrid assay was disrupted by P194A, L193A/P194A, and L193A/P194A/T204D, but not L193A or T204D alone. Thus, FKBP12 recognition is dispensable for TGFbeta signaling.
Publication types
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Amino Acid Isomerases / metabolism*
-
Amino Acid Sequence
-
Carrier Proteins / metabolism*
-
Cells, Cultured
-
DNA Mutational Analysis
-
DNA-Binding Proteins / metabolism*
-
Heat-Shock Proteins / metabolism*
-
Molecular Sequence Data
-
Protein Binding
-
Protein Serine-Threonine Kinases / metabolism*
-
Receptors, Transforming Growth Factor beta / metabolism*
-
Signal Transduction
-
Structure-Activity Relationship
-
Tacrolimus Binding Proteins
-
Transforming Growth Factor beta / metabolism*
Substances
-
Carrier Proteins
-
DNA-Binding Proteins
-
Heat-Shock Proteins
-
Receptors, Transforming Growth Factor beta
-
Transforming Growth Factor beta
-
XTrR-I receptor
-
Protein Serine-Threonine Kinases
-
Amino Acid Isomerases
-
Tacrolimus Binding Proteins