DOI: 10.1073/pnas.190276697. The proliferative and antiapoptotic effects of substance P are facilitated by formation of a β-arrestin-dependent scaffolding complex

The proliferative and antiapoptotic effects of substance P are facilitated by formation of a β-arrestin-dependent scaffolding complex

10.1073/pnas.190276697

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

A requirement for scaffolding complexes containing internalized G protein-coupled receptors and β-arrestins in the activation and subcellular localization of extracellular signal-regulated kinases 1 and 2 (ERK1/2) has recently been proposed. However, the composition of these complexes and the importance of this requirement for function of ERK1/2 appear to differ between receptors. Here we report that substance P (SP) activation of neurokinin-1 receptor (NK1R) stimulates the formation of a scaffolding complex comprising internalized receptor, β-arrestin, src, and ERK1/2 (detected by gel filtration, immunoprecipitation, and immunofluorescence). Inhibition of complex formation, by expression of dominant-negative β-arrestin or a truncated NK1R that fails to interact with β-arrestin, inhibits both SP-stimulated endocytosis of the NK1R and activation of ERK1/2, which is required for the proliferative and antiapoptotic effects of SP. Thus, formation of a β-arrestin-containing complex facilitates the proliferative and antiapoptotic effects of SP, and these effects of SP could be diminished in cells expressing truncated NK1R corresponding to a naturally occurring variant.

Bibliography

DeFea, K. A., Vaughn, Z. D., OâBryan, E. M., Nishijima, D., DÃ©ry, O., & Bunnett, N. W. (2000). The proliferative and antiapoptotic effects of substance P are facilitated by formation of a Î²-arrestin-dependent scaffolding complex. Proceedings of the National Academy of Sciences, 97(20), 11086â11091.

Authors 6

K. A. DeFea (first)
Z. D. Vaughn (additional)
E. M. O'Bryan (additional)
D. Nishijima (additional)
O. Déry (additional)
N. W. Bunnett (additional)

References 34 Referenced 342

Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:32 a.m.)
Deposited	2 years, 4 months ago (April 22, 2023, 8:07 a.m.)
Indexed	6 days, 1 hour ago (Aug. 29, 2025, 6:33 a.m.)
Issued	24 years, 11 months ago (Sept. 19, 2000)
Published	24 years, 11 months ago (Sept. 19, 2000)
Published Online	24 years, 11 months ago (Sept. 19, 2000)
Published Print	24 years, 11 months ago (Sept. 26, 2000)

Funders 0

None

BibTeX

@article{DeFea_2000, title={The proliferative and antiapoptotic effects of substance P are facilitated by formation of a β-arrestin-dependent scaffolding complex}, volume={97}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.190276697}, DOI={10.1073/pnas.190276697}, number={20}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={DeFea, K. A. and Vaughn, Z. D. and O’Bryan, E. M. and Nishijima, D. and Déry, O. and Bunnett, N. W.}, year={2000}, month=sep, pages={11086–11091} }

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