TGF-β Superfamily Signaling in Embryonic Development and Homeostasis receptor levels regulate the specificity of signaling pathway activation and biological effects of TGF-β Superfamily Signaling in Embryonic Development and Homeostasis

Abstract

TGF-?? is a pluripotent cytokine that mediates its effects through a receptor composed of TGF-?? receptor type II (TGFBR2) and type I (TGFBR1). The TGF-?? receptor can regulate Smad and nonSmad signaling pathways, which then ultimately dictate TGF-??'s biological effects. We postulated that control of the level of TGFBR2 is a mechanism for regulating the specificity of TGF-?? signaling pathway activation and TGF-??'s biological effects. We used a precisely regulatable TGFBR2 expression system to assess the effects of TGFBR2 expression levels on signaling and TGF-?? mediated apoptosis. We found Smad signaling and MAPK-ERK signaling activation levels correlate directly with TGFBR2 expression levels. Furthermore, p21 levels and TGF-?? 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-?? signaling pathways appears to be a mechanism for regulating the specificity of the biological effects of TGF-??. ?? 2009 Elsevier B.V. All rights reserved.