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 (T beta R-I). As the FK506 motif that competes with T beta R-I for FKBP12 resembles an invariant Leu-Pro dipeptide in T beta R-I, we replaced Leu(193) and Pro(194) with Ala, along with mutations across the Gly/Ser box. L193A, P194A, and L193A/P194A do not alter T beta R-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 TGF beta signaling.