FKBP-12 recognition is dispensable for signal generation by type I transforming growth factor-beta receptors

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 acr...

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Bibliographic Details
Published in:The Journal of biological chemistry 1996-09, Vol.271 (38), p.22941-22944
Main Authors: Charng, M J, Kinnunen, P, Hawker, J, Brand, T, Schneider, M D
Format: Article
Language:English
Subjects:
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
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Summary: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.
ISSN:0021-9258
DOI:10.1074/jbc.271.38.22941