TY - JOUR
T1 - FKBP12 is a negative regulator of transforming growth factor-β receptor internalization
AU - Yao, Diying
AU - Doré, Jules J.E.
AU - Leof, Edward B.
PY - 2000/4/28
Y1 - 2000/4/28
N2 - 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.
AB - 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.
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U2 - 10.1074/jbc.275.17.13149
DO - 10.1074/jbc.275.17.13149
M3 - Article
C2 - 10777621
AN - SCOPUS:0034725060
SN - 0021-9258
VL - 275
SP - 13149
EP - 13154
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 17
ER -