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Beta-arrestin 2 mediates endocytosis of type III TGF-beta receptor and down-regulation of its signaling.

Publication ,  Journal Article
Chen, W; Kirkbride, KC; How, T; Nelson, CD; Mo, J; Frederick, JP; Wang, X-F; Lefkowitz, RJ; Blobe, GC
Published in: Science
September 5, 2003

beta-Arrestins bind to activated seven transmembrane-spanning (7TMS) receptors (G protein-coupled receptors) after the receptors are phosphorylated by G protein-coupled receptor kinases (GRKs), thereby regulating their signaling and internalization. Here, we demonstrate an unexpected and analogous role of beta-arrestin 2 (betaarr2) for the single transmembrane-spanning type III transforming growth factor-beta (TGF-beta) receptor (TbetaRIII, also referred to as betaglycan). Binding of betaarr2 to TbetaRIII was also triggered by phosphorylation of the receptor on its cytoplasmic domain (likely at threonine 841). However, such phosphorylation was mediated by the type II TGF-beta receptor (TbetaRII), which is itself a kinase, rather than by a GRK. Association with betaarr2 led to internalization of both receptors and down-regulation of TGF-beta signaling. Thus, the regulatory actions of beta-arrestins are broader than previously appreciated, extending to the TGF-beta receptor family as well.

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Published In

Science

DOI

EISSN

1095-9203

Publication Date

September 5, 2003

Volume

301

Issue

5638

Start / End Page

1394 / 1397

Location

United States

Related Subject Headings

  • beta-Arrestins
  • beta-Arrestin 2
  • Transforming Growth Factor beta1
  • Transforming Growth Factor beta
  • Transfection
  • Signal Transduction
  • Recombinant Fusion Proteins
  • Receptors, Transforming Growth Factor beta
  • Receptor, Transforming Growth Factor-beta Type II
  • RNA, Small Interfering
 

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Chen, W., Kirkbride, K. C., How, T., Nelson, C. D., Mo, J., Frederick, J. P., … Blobe, G. C. (2003). Beta-arrestin 2 mediates endocytosis of type III TGF-beta receptor and down-regulation of its signaling. Science, 301(5638), 1394–1397. https://doi.org/10.1126/science.1083195
Chen, Wei, Kellye C. Kirkbride, Tam How, Christopher D. Nelson, Jinyao Mo, Joshua P. Frederick, Xiao-Fan Wang, Robert J. Lefkowitz, and Gerard C. Blobe. “Beta-arrestin 2 mediates endocytosis of type III TGF-beta receptor and down-regulation of its signaling.Science 301, no. 5638 (September 5, 2003): 1394–97. https://doi.org/10.1126/science.1083195.
Chen W, Kirkbride KC, How T, Nelson CD, Mo J, Frederick JP, et al. Beta-arrestin 2 mediates endocytosis of type III TGF-beta receptor and down-regulation of its signaling. Science. 2003 Sep 5;301(5638):1394–7.
Chen, Wei, et al. “Beta-arrestin 2 mediates endocytosis of type III TGF-beta receptor and down-regulation of its signaling.Science, vol. 301, no. 5638, Sept. 2003, pp. 1394–97. Pubmed, doi:10.1126/science.1083195.
Chen W, Kirkbride KC, How T, Nelson CD, Mo J, Frederick JP, Wang X-F, Lefkowitz RJ, Blobe GC. Beta-arrestin 2 mediates endocytosis of type III TGF-beta receptor and down-regulation of its signaling. Science. 2003 Sep 5;301(5638):1394–1397.
Journal cover image

Published In

Science

DOI

EISSN

1095-9203

Publication Date

September 5, 2003

Volume

301

Issue

5638

Start / End Page

1394 / 1397

Location

United States

Related Subject Headings

  • beta-Arrestins
  • beta-Arrestin 2
  • Transforming Growth Factor beta1
  • Transforming Growth Factor beta
  • Transfection
  • Signal Transduction
  • Recombinant Fusion Proteins
  • Receptors, Transforming Growth Factor beta
  • Receptor, Transforming Growth Factor-beta Type II
  • RNA, Small Interfering