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 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.
Charng
M J
MJ
Department of Medicine, Baylor College of Medicine, Houston, Texas 77030, USA.
Kinnunen
P
P
Hawker
J
J
Brand
T
T
Schneider
M D
MD
D000591:Amino Acid Isomerases / Q000378:metabolism*; D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D022021:Tacrolimus Binding Proteins; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D006360:Heat-Shock Proteins; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; C094515:XTrR-I receptor; D017346:Protein Serine-Threonine Kinases; D000591:Amino Acid Isomerases; D022021:Tacrolimus Binding Proteins