Open Access
The immunophilin FKBP12: a molecular guardian of the TGF-beta family type I receptors
Tongwen Wang1,Patricia K Donahoe1
The Benaroya Research Institute at Virginia Mason, 1201 9th Avenue, Seattle, WA 98101, USA.
DOI: 10.2741/1095 Volume 9 Issue 1, pp.619-631
Published: 01 January 2004
(This article belongs to the Special Issue TGFbeta,BMP receptor signaling)

FKBP12 as an immunophilin that binds to two well-known immunosuppressive macrolides, FK506 and rapamycin, has attracted immense attention and its role in mediating the immunosuppressive functions of these macrolides has been extensively studied. Since FKBP12 is a well-conserved protein among many species and is also highly expressed in almost all cells, it must play important roles in cellular function in the absence of macrolides. In one such a role, FKBP12 interacts with and regulates the functional state of the ryanodine Ca2+ channel receptor by altering protein conformation and coordinating multi-protein complex formation. This review summarizes another physiological role of FKBP12 as an interactor and a regulator of the type I serine/threonine kinase receptors of TGF-beta superfamily. Current data, derived from detailed biochemical studies as well as from functional studies in various systems, suggest that FKBP12 functions as a "guardian" for the type I receptors to prevent them from leaky signaling under sub-optimal ligand concentrations, thereby providing a molecular "gradient reader" for TGF-beta family morphogens. This aspect of FKBP12 function may be critical for cellular responsiveness to morphogenetic gradients of the TGF-beta family members during early development, serving to assure the translation of different ligand concentrations into different signaling readouts.

Share and Cite
Tongwen Wang, Patricia K Donahoe. The immunophilin FKBP12: a molecular guardian of the TGF-beta family type I receptors. Frontiers in Bioscience-Landmark. 2004. 9(1); 619-631.