FKBP12 is not required for the modulation of transforming growth factor beta receptor I signaling activity in embryonic fibroblasts and thymocytes.

Journal Article (Journal Article)

Transforming growth factor beta (TGF-beta) signals through a heteromeric complex of type I and type II transmembrane serine-threonine kinases. 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 FKBP12 inhibits type I receptor phosphorylation by the type II receptor. To determine the physiological relevance of the FKBP12-TGF-beta receptor I interaction, we investigated whether disruption of this interaction 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 inhibition. Dose-response curves for TGF-beta-mediated signaling in primary fibroblasts and thymocytes isolated from either wild-type or FKBP12-deficient mice were identical. Taken together, our results indicate that FKBP12 does not play a unique physiological role in TGF-beta signaling in primary fibroblasts and thymocytes.

Full Text

Duke Authors

Cited Authors

  • Bassing, CH; Shou, W; Muir, S; Heitman, J; Matzuk, MM; Wang, XF

Published Date

  • March 1, 1998

Published In

Volume / Issue

  • 9 / 3

Start / End Page

  • 223 - 228

PubMed ID

  • 9543388

International Standard Serial Number (ISSN)

  • 1044-9523


  • eng

Conference Location

  • United States