转化生长因子-β受体水平调节转化生长因子-β信号通路激活的特异性和生物学效应。
TGF-beta receptor levels regulate the specificity of signaling pathway activation and biological effects of TGF-beta.
作者信息
Rojas Andres, Padidam Malla, Cress Dean, Grady William M
机构信息
Clinical Research Division, Fred Hutchinson Cancer Research Center, WA 98109, USA.
出版信息
Biochim Biophys Acta. 2009 Jul;1793(7):1165-73. doi: 10.1016/j.bbamcr.2009.02.001. Epub 2009 Feb 12.
Abstract
TGF-beta is a pluripotent cytokine that mediates its effects through a receptor composed of TGF-beta receptor type II (TGFBR2) and type I (TGFBR1). The TGF-beta receptor can regulate Smad and nonSmad signaling pathways, which then ultimately dictate TGF-beta's biological effects. We postulated that control of the level of TGFBR2 is a mechanism for regulating the specificity of TGF-beta signaling pathway activation and TGF-beta's biological effects. We used a precisely regulatable TGFBR2 expression system to assess the effects of TGFBR2 expression levels on signaling and TGF-beta mediated apoptosis. We found Smad signaling and MAPK-ERK signaling activation levels correlate directly with TGFBR2 expression levels. Furthermore, p21 levels and TGF-beta 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-beta signaling pathways appears to be a mechanism for regulating the specificity of the biological effects of TGF-beta.
摘要
转化生长因子-β（TGF-β）是一种多能细胞因子，它通过由II型转化生长因子-β受体（TGFBR2）和I型受体（TGFBR1）组成的受体介导其效应。TGF-β受体可调节Smad和非Smad信号通路，最终决定TGF-β的生物学效应。我们推测，控制TGFBR2的水平是调节TGF-β信号通路激活特异性和TGF-β生物学效应的一种机制。我们使用了一个精确可调节的TGFBR2表达系统来评估TGFBR2表达水平对信号传导和TGF-β介导的细胞凋亡的影响。我们发现Smad信号传导和MAPK-ERK信号激活水平与TGFBR2表达水平直接相关。此外，p21水平和TGF-β诱导的细胞凋亡似乎依赖于相对较高的TGFBR2表达以及MAPK-ERK和Smad通路的激活。因此，控制TGFBR2表达和TGF-β信号通路的差异激活似乎是调节TGF-β生物学效应特异性的一种机制。
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