The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.
Activity-Dependent Internalization of Smoothened Mediated by ß-Arrestin 2 and GRK2
Abstract
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 β-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 β-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 β-arrestin 2 with Smo. β-Arrestin 2 and GRK2 are thus potential mediators of signaling by activated Smo.
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Citations
Cites
Patched acts catalytically to suppress the activity of Smoothened
Taipale, J., Cooper, M. K., Maiti, T., & Beachy, P. A. (2002) · Nature · doi:10.1038/nature00989 · Cited by 794
Self-citationOakley, R. H., Laporte, S. A., Holt, J. A., Barak, L. S., & Caron, M. G. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m101450200 · Cited by 455
Cited by
The mechanisms of Hedgehog signalling and its roles in development and disease
Briscoe, J., & Thérond, P. P. (2013) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3598 · Cited by 1,751
Vertebrate Smoothened functions at the primary cilium
Corbit, K. C., Aanstad, P., Singla, V., Norman, A. R., Stainier, D. Y. R., & Reiter, J. F. (2005) · Nature · doi:10.1038/nature04117 · Cited by 1,481
Gavard, J., & Gutkind, J. S. (2006) · Nature Cell Biology · doi:10.1038/ncb1486 · Cited by 1,018
Beyond Desensitization: Physiological Relevance of Arrestin-Dependent Signaling
Luttrell, L. M., Gesty-Palmer, D., & Sibley, D. R. (2010) · Pharmacological Reviews · doi:10.1124/pr.109.002436 · Cited by 369
New Roles for β-Arrestins in Cell Signaling: Not Just for Seven-Transmembrane Receptors
Lefkowitz, R. J., Rajagopal, K., & Whalen, E. J. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.11.007 · Cited by 301
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Metadata
- Authors
- Chen, W., Ren, X.-R., Nelson, C. D., Barak, L. S., Chen, J. K., Beachy, P. A., de Sauvage, F., & Lefkowitz, R. J.
- Venue
- Science
- Published
- 2004-12-24
- Volume
- 306
- Issue
- 5705
- Pages
- 2257-2260
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2053996795
- Cited by
- 279
- References
- 2
- FWCI
- 6.45
- Type
- journal article
- Language
- en
- Open access
- closed
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- Chen, W., Ren, X.-R., Nelson, C. D., Barak, L. S., Chen, J. K., Beachy, P. A., de Sauvage, F., & Lefkowitz, R. J. (2004). Activity-Dependent Internalization of Smoothened Mediated by ß-Arrestin 2 and GRK2. Science. https://doi.org/10.1126/science.1104135
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