FKBP12 is a negative regulator of transforming growth factor-β receptor internalization

Diying Yao, Jules J.E. Doré, Edward B. Leof

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

Transforming growth factor-β (TGF-β) family polypeptides regulate cell growth and differentiation by binding to single pass serine/threonine kinases referred to as TGF-β type I and II receptors. Although interaction screens have shown that the immunophilin FKBP12 interacts with TGF-β type I receptors, the role of FKBP12 in TGF-β receptor action is presently unclear. Using a chimeric TGF-β receptor system, we have shown a specific enhancement of internalization when FKBP12 binding to the type I receptor was prevented with rapamycin. Moreover, although earlier studies demonstrated that type II receptor kinase activity was required for optimal internalization in mesenchymal cells, we found that rapamycin functioned downstream of the type II receptor kinase. Thus, rather than modulating TGF-β signaling, our data suggest a novel role for FKBP12 as a negative regulator of TGF-β receptor endocytosis.

Original languageEnglish (US)
Pages (from-to)13149-13154
Number of pages6
JournalJournal of Biological Chemistry
Volume275
Issue number17
DOIs
StatePublished - Apr 28 2000

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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