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Endocytosis of the type III transforming growth factor-beta (TGF-beta) receptor through the clathrin-independent/lipid raft pathway regulates TGF-beta signaling and receptor down-regulation.

Publication ,  Journal Article
Finger, EC; Lee, NY; You, H-J; Blobe, GC
Published in: J Biol Chem
December 12, 2008

Transforming growth factor-beta (TGF-beta) signals through three highly conserved cell surface receptors, the type III TGF-beta receptor (T beta RIII), the type II TGF-beta receptor (T beta RII), and the type I TGF-beta receptor (T beta RI) to regulate diverse cellular processes including cell proliferation, differentiation, migration, and apoptosis. Although T beta RI and T beta RII undergo ligand-independent endocytosis by both clathrin-mediated endocytosis, resulting in enhanced signaling, and clathrin-independent endocytosis, resulting in receptor degradation, the mechanism and function of T beta RIII endocytosis is poorly understood. T beta RIII is a heparan sulfate proteoglycan with a short cytoplasmic tail that functions as a TGF-beta superfamily co-receptor, contributing to TGF-beta signaling through mechanisms yet to be fully defined. We have reported previously that T beta RIII endocytosis, mediated by a novel interaction with beta arrestin-2, results in decreased TGF-beta signaling. Here we demonstrate that T beta RIII undergoes endocytosis in a ligand and glycosaminoglycan modification-independent and cytoplasmic domain-dependent manner, with the interaction of Thr-841 in the cytoplasmic domain of T beta RIII with beta-arrestin2 enhancing T beta RIII endocytosis. T beta RIII undergoes both clathrin-mediated and clathrin-independent endocytosis. Importantly, inhibition of the clathrin-independent, lipid raft pathway, but not of the clathrin-dependent pathway, results in decreased TGF-beta1 induced Smad2 and p38 phosphorylation, supporting a specific role for clathrin-independent endocytosis of T beta RIII in regulating both Smad-dependent and Smad-independent TGF-beta signaling.

Duke Scholars

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

December 12, 2008

Volume

283

Issue

50

Start / End Page

34808 / 34818

Location

United States

Related Subject Headings

  • Transforming Growth Factor beta
  • Signal Transduction
  • Receptors, Transforming Growth Factor beta
  • Proteoglycans
  • Models, Biological
  • Membrane Microdomains
  • Ligands
  • Humans
  • Glycosaminoglycans
  • Endocytosis
 

Citation

APA
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Finger, E. C., Lee, N. Y., You, H.-J., & Blobe, G. C. (2008). Endocytosis of the type III transforming growth factor-beta (TGF-beta) receptor through the clathrin-independent/lipid raft pathway regulates TGF-beta signaling and receptor down-regulation. J Biol Chem, 283(50), 34808–34818. https://doi.org/10.1074/jbc.M804741200
Finger, Elizabeth C., Nam Y. Lee, Hye-jin You, and Gerard C. Blobe. “Endocytosis of the type III transforming growth factor-beta (TGF-beta) receptor through the clathrin-independent/lipid raft pathway regulates TGF-beta signaling and receptor down-regulation.J Biol Chem 283, no. 50 (December 12, 2008): 34808–18. https://doi.org/10.1074/jbc.M804741200.
Finger, Elizabeth C., et al. “Endocytosis of the type III transforming growth factor-beta (TGF-beta) receptor through the clathrin-independent/lipid raft pathway regulates TGF-beta signaling and receptor down-regulation.J Biol Chem, vol. 283, no. 50, Dec. 2008, pp. 34808–18. Pubmed, doi:10.1074/jbc.M804741200.

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

December 12, 2008

Volume

283

Issue

50

Start / End Page

34808 / 34818

Location

United States

Related Subject Headings

  • Transforming Growth Factor beta
  • Signal Transduction
  • Receptors, Transforming Growth Factor beta
  • Proteoglycans
  • Models, Biological
  • Membrane Microdomains
  • Ligands
  • Humans
  • Glycosaminoglycans
  • Endocytosis