Skip to main content
Journal cover image

Activity-dependent internalization of smoothened mediated by beta-arrestin 2 and GRK2.

Publication ,  Journal Article
Chen, W; Ren, X-R; Nelson, CD; Barak, LS; Chen, JK; Beachy, PA; de Sauvage, F; Lefkowitz, RJ
Published in: Science
December 24, 2004

Binding of Sonic Hedgehog (Shh) to Patched (Ptc) relieves the latter's tonic inhibition of Smoothened (Smo), a receptor that spans the cell membrane seven times. This initiates signaling which, by unknown mechanisms, regulates vertebrate developmental processes. We find that two molecules interact with mammalian Smo in an activation-dependent manner: G protein-coupled receptor kinase 2 (GRK2) leads to phosphorylation of Smo, and beta-arrestin 2 fused to green fluorescent protein interacts with Smo. These two processes promote endocytosis of Smo in clathrin-coated pits. Ptc inhibits association of beta-arrestin 2 with Smo, and this inhibition is relieved in cells treated with Shh. A Smo agonist stimulated and a Smo antagonist (cyclopamine) inhibited both phosphorylation of Smo by GRK2 and interaction of beta-arrestin 2 with Smo. beta-Arrestin 2 and GRK2 are thus potential mediators of signaling by activated Smo.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Science

DOI

EISSN

1095-9203

Publication Date

December 24, 2004

Volume

306

Issue

5705

Start / End Page

2257 / 2260

Location

United States

Related Subject Headings

  • beta-Arrestins
  • beta-Arrestin 2
  • beta-Adrenergic Receptor Kinases
  • Veratrum Alkaloids
  • Transfection
  • Trans-Activators
  • Thiophenes
  • Smoothened Receptor
  • Signal Transduction
  • Recombinant Fusion Proteins
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Chen, W., Ren, X.-R., Nelson, C. D., Barak, L. S., Chen, J. K., Beachy, P. A., … Lefkowitz, R. J. (2004). Activity-dependent internalization of smoothened mediated by beta-arrestin 2 and GRK2. Science, 306(5705), 2257–2260. https://doi.org/10.1126/science.1104135
Chen, Wei, Xiu-Rong Ren, Christopher D. Nelson, Larry S. Barak, James K. Chen, Philip A. Beachy, Frederic de Sauvage, and Robert J. Lefkowitz. “Activity-dependent internalization of smoothened mediated by beta-arrestin 2 and GRK2.Science 306, no. 5705 (December 24, 2004): 2257–60. https://doi.org/10.1126/science.1104135.
Chen W, Ren X-R, Nelson CD, Barak LS, Chen JK, Beachy PA, et al. Activity-dependent internalization of smoothened mediated by beta-arrestin 2 and GRK2. Science. 2004 Dec 24;306(5705):2257–60.
Chen, Wei, et al. “Activity-dependent internalization of smoothened mediated by beta-arrestin 2 and GRK2.Science, vol. 306, no. 5705, Dec. 2004, pp. 2257–60. Pubmed, doi:10.1126/science.1104135.
Chen W, Ren X-R, Nelson CD, Barak LS, Chen JK, Beachy PA, de Sauvage F, Lefkowitz RJ. Activity-dependent internalization of smoothened mediated by beta-arrestin 2 and GRK2. Science. 2004 Dec 24;306(5705):2257–2260.
Journal cover image

Published In

Science

DOI

EISSN

1095-9203

Publication Date

December 24, 2004

Volume

306

Issue

5705

Start / End Page

2257 / 2260

Location

United States

Related Subject Headings

  • beta-Arrestins
  • beta-Arrestin 2
  • beta-Adrenergic Receptor Kinases
  • Veratrum Alkaloids
  • Transfection
  • Trans-Activators
  • Thiophenes
  • Smoothened Receptor
  • Signal Transduction
  • Recombinant Fusion Proteins