TGF beta receptor internalization into EEA1-enriched early endosomes: role in signaling to Smad2.
TGF beta receptor internalization into EEA1-enriched early endosomes: role in signaling to Smad2.
复制标题
DOI：
10.1083/jcb.200204088
复制
发表时间：
2002-09-30
期刊：
影响因子：
--
通讯作者：
Corvera S
中科院分区：
文献类型：
--
作者：
Hayes S;Chawla A;Corvera S
转化生长因子（Transforming growth factor，TGF）β是细胞生长和分化的重要生理调节因子。它激活受体苏氨酸/丝氨酸激酶，磷酸化转录因子Smad 2，然后易位到细胞核中触发特定的转录事件。在这里，我们表明，激活的I型和II型TGFβ受体内化到含有早期内体蛋白EEA 1的内体中。TGFβ刺激Smad 2磷酸化、Smad 2核转位和TGFβ刺激转录的程度与受体内化的程度密切相关。TGFβ信号传导还需要SARA（用于受体活化的Smad锚），一种含有FYVE Zn++指基序的135-kD多肽。我们发现SARA定位于含有EEA 1的核内体，并且这种定位的破坏抑制TGFβ诱导的Smad 2核转位。这些结果表明，TGFβ受体进入内体的运输使TGFβ信号传导成为可能，揭示了内体作为专门用于放大某些细胞外信号的隔室的新功能。
Transforming growth factor (TGF)β is an important physiological regulator of cellular growth and differentiation. It activates a receptor threonine/serine kinase that phosphorylates the transcription factor Smad2, which then translocates into the nucleus to trigger specific transcriptional events. Here we show that activated type I and II TGFβ receptors internalize into endosomes containing the early endosomal protein EEA1. The extent of TGFβ-stimulated Smad2 phosphorylation, Smad2 nuclear translocation, and TGFβ-stimulated transcription correlated closely with the extent of internalization of the receptor. TGFβ signaling also requires SARA (Smad anchor for receptor activation), a 135-kD polypeptide that contains a FYVE Zn++ finger motif. Here we show that SARA localizes to endosomes containing EEA1, and that disruption of this localization inhibits TGFβ-induced Smad2 nuclear translocation. These results indicate that traffic of the TGFβ receptor into the endosome enables TGFβ signaling, revealing a novel function for the endosome as a compartment specialized for the amplification of certain extracellular signals.
登录
查看更多内容
影响因子：
5.3
作者：
Lebrun, JJ;Vale, WW
通讯作者：
Vale, WW
影响因子：
3.3
作者：
Wilson, JM;de Hoop, M;Parton, RG
通讯作者：
Parton, RG
影响因子：
4.8
作者：
Panopoulou, E;Gillooly, DJ;Fotsis, T
通讯作者：
Fotsis, T
影响因子：
4.8
作者：
Stenmark, H;Aasland, R;DArrigo, A
通讯作者：
DArrigo, A
影响因子：
64.5
作者：
Entchev, EV;Schwabedissen, A;González-Gaitán, M
通讯作者：
González-Gaitán, M