期刊
JOURNAL OF CELL BIOLOGY
卷 158, 期 7, 页码 1239-1249出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.200204088
关键词
FYVE; PI 3-kinase; transforming growth factor; SARA; endocytosis
类别
资金
- NIDDK NIH HHS [DK54479, R01 DK054479] Funding Source: Medline
Transforming growth factor (TGF)beta 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 11 TGFbeta receptors internalize into endosomes containing the early endosomal protein EEA1. The extent of TGFbeta-stimulated Smad2 phosphorylation, Smad2 nuclear translocation, and TGFbeta-stimulated transcription correlated closely with the extent of internalization of the receptor. TGFbeta 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 TGFbeta-induced Smad2 nuclear translocation. These results indicate that traffic of the TGFbeta receptor into the endosome enables TGFbeta signaling, revealing a novel function for the endosome as a compartment specialized for the amplification of certain extracellular signals.
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