FKBP12 IS NOT REQUIRED FOR THE MODULATION OF TRANSFORMING-GROWTH-FACTOR-BETA RECEPTOR-I SIGNALING ACTIVITY IN EMBRYONIC FIBROBLASTS AND THYMOCYTES

Transforming growth factor beta (TGF-beta) signals through a heteromer ic complex of type I and type II transmembrane serine-threonine kinase s. Recent evidence suggests that the immunophilin FKBP12 modulates the activity of the type I receptor, based on data that immunosuppressive drugs that disrupt FKBP12 binding to the type I receptor enhance TGF- beta signaling in mink lung epithelial cells, and overexpression of FK BP12 inhibits type I receptor phosphorylation by the type II receptor, To determine the physiological relevance of the FKBP12-TGF-beta recep tor I interaction, we investigated whether disruption of this interact ion affects TGF-beta-signaling in primary mouse embryo fibroblasts and thymocytes, We found that the addition of excess drugs had no effect on either TGF-beta-mediated transcriptional responses or growth inhibi tion, Dose-response curves for TGF-beta-mediated signaling in primary fibroblasts and thymocytes isolated from either wild-type or FKBP12-de ficient mice were identical. Taken together, our results indicate that FKBP12 does not play a unique physiological role in TGF-beta signalin g in primary fibroblasts and thymocytes.