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PMID: 10995467 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

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

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 97 ·No. 20 ·2000-09-26 ·Pages 11086-91

DeFea KA, Vaughn ZD, O'Bryan EM, Nishijima D, Déry O, Bunnett NW

Abstract

A requirement for scaffolding complexes containing internalized G protein-coupled receptors and beta-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, beta-arrestin, src, and ERK1/2 (detected by gel filtration, immunoprecipitation, and immunofluorescence). Inhibition of complex formation, by expression of dominant-negative beta-arrestin or a truncated NK1R that fails to interact with beta-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 beta-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.

MeSH Terms
Animals Apoptosis/drug effects,physiology Arrestins/physiology Cell Division/drug effects,physiology Cell Line MAP Kinase Signaling System Rats Receptors, Neurokinin-1/physiology Signal Transduction/drug effects Substance P/pharmacology beta-Arrestins
Chemicals
Arrestins Receptors, Neurokinin-1 beta-Arrestins Substance P
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
DeFea K A
Department of Surgery, University of California, San Francisco, 521 Parnassus Avenue, San Francisco, CA 94143-0660, USA.
Vaughn Z D
O'Bryan E M
Nishijima D
Déry O
Bunnett N W
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.190276697
Published
2000-09-26
Pages
11086-91
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC27152
Subset
IM
Grants
NIDDK NIH HHS · R01 DK039957 · United States
NIDDK NIH HHS · R37 DK039957 · United States
NIDDK NIH HHS · DK39957 · United States
External Links
PubMed source DOI: 10.1073/pnas.190276697 PMC Full Text View journal details
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