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J Cell Biol. 2002 Sep 30;158(7):1239-49.

TGF beta receptor internalization into EEA1-enriched early endosomes: role in signaling to Smad2.

Author information

  • 1Program in Molecular Medicine and Interdisciplinary Graduate Program, University of Massachusetts Medical School, Worcester, MA 01605, USA.

Abstract

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 II TGF beta receptors internalize into endosomes containing the early endosomal protein EEA1. The extent of TGF beta-stimulated Smad2 phosphorylation, Smad2 nuclear translocation, and TGF beta-stimulated transcription correlated closely with the extent of internalization of the receptor. TGF beta 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 TGF beta-induced Smad2 nuclear translocation. These results indicate that traffic of the TGF beta receptor into the endosome enables TGF beta signaling, revealing a novel function for the endosome as a compartment specialized for the amplification of certain extracellular signals.

PMID:
12356868
[PubMed - indexed for MEDLINE]
PMCID:
PMC2173232
Free PMC Article

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