TGF-ß receptor levels regulate the specificity of signaling pathway activation and biological effects of TGF-ß
Por:
Rojas A., Padidam M., Cress D., Grady W.M.
Publicada:
1 ene 2009
Resumen:
TGF-ß is a pluripotent cytokine that mediates its effects through a receptor composed of TGF-ß receptor type II (TGFBR2) and type I (TGFBR1). The TGF-ß receptor can regulate Smad and nonSmad signaling pathways, which then ultimately dictate TGF-ß's biological effects. We postulated that control of the level of TGFBR2 is a mechanism for regulating the specificity of TGF-ß signaling pathway activation and TGF-ß's biological effects. We used a precisely regulatable TGFBR2 expression system to assess the effects of TGFBR2 expression levels on signaling and TGF-ß mediated apoptosis. We found Smad signaling and MAPK-ERK signaling activation levels correlate directly with TGFBR2 expression levels. Furthermore, p21 levels and TGF-ß induced apoptosis appear to depend on relatively high TGFBR2 expression and on the activation of the MAPK-ERK and Smad pathways. Thus, control of TGFBR2 expression and the differential activation of TGF-ß signaling pathways appears to be a mechanism for regulating the specificity of the biological effects of TGF-ß. © 2009 Elsevier B.V. All rights reserved.
Filiaciones:
Rojas A.:
Clinical Research Division, Fred Hutchinson Cancer Research Center, United States
Department of Cancer Biology, Vanderbilt University Medical School, Nashville, TN, United States
Padidam M.:
Intrexon Corporation, Blacksburg, VA, United States
Cress D.:
Intrexon Corporation, Blacksburg, VA, United States
Grady W.M.:
Clinical Research Division, Fred Hutchinson Cancer Research Center, United States
Department of Cancer Biology, Vanderbilt University Medical School, Nashville, TN, United States
Department of Medicine, University of Washington Medical School, United States
R and D Service, Puget Sound VA Healthcare system, Seattle WA, United States
|