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PMID: 12356868 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

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

The Journal of cell biology ·Vol. 158 ·No. 7 ·2002-09-30 ·Pages 1239-49

Hayes S, Chawla A, Corvera S

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.

MeSH Terms
Animals Binding Sites COS Cells Carrier Proteins/metabolism Cricetinae DNA-Binding Proteins/physiology Dynamins/genetics,metabolism Endosomes/metabolism Fluorescent Antibody Technique Genes, Dominant/physiology HeLa Cells Humans Intracellular Signaling Peptides and Proteins Membrane Proteins/metabolism Phosphorylation Potassium/metabolism Protein Transport Receptors, Transforming Growth Factor beta/metabolism Serine Endopeptidases Signal Transduction/physiology Smad2 Protein Subcellular Fractions Trans-Activators/physiology Transfection Transferrin/metabolism Transforming Growth Factor beta/metabolism Tumor Cells, Cultured/cytology Vesicular Transport Proteins Zinc Fingers
Chemicals
Carrier Proteins DNA-Binding Proteins Intracellular Signaling Peptides and Proteins Membrane Proteins Receptors, Transforming Growth Factor beta SMAD2 protein, human Smad2 Protein Trans-Activators Transferrin Transforming Growth Factor beta Vesicular Transport Proteins early endosome antigen 1 ZFYVE16 protein, human Serine Endopeptidases Dynamins Potassium
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Hayes Susan
Program in Molecular Medicine and Interdisciplinary Graduate Program, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Chawla Anil
Corvera Silvia
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.200204088
Published
2002-09-30
Pages
1239-49
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2173232
Subset
IM
Grants
NIDDK NIH HHS · R01 DK054479 · United States
NIDDK NIH HHS · DK54479 · United States
External Links
PubMed source DOI: 10.1083/jcb.200204088 PMC Full Text View journal details
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