Model depicting FKBP12 regulation of type I TGF-β receptor signaling.
(Left) In FKBP12+/+ cells, TGF-β1 induces
gene transcription by SMAD2/3, p38, and ERK MAP kinase leading to
induction of p21, SMAD7, PAI-1, and other genes under the influence of
TGF-β receptor signaling. (Upper Right)
FKBP12−/− cells are partially activated in a
ligand-independent manner leading to augmentation of p21, SMAD7, and
p38. (Lower Right) TGF-β1 treatment of the
FKBP12−/− cells cannot further induce or activate these
pathways due to feedback influenced by SMAD7. PAI-1 is basally
activated in FKBP12−/− cells and can be further activated
by TGF-β1.