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Interchanging the C‐termini of PAR‐2 and NK1R leads to specific β‐arrestin signaling events
Author(s) -
Mathur Maneesh,
Kumar Puneet,
Lau Michael,
DeFea Kathryn
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a982-c
Subject(s) - g protein coupled receptor , arrestin , microbiology and biotechnology , receptor , signal transduction , chemistry , extracellular , kinase , biology , biochemistry
Some G‐protein coupled receptors (GPCRs) can activate extracellular signal regulated kinases 1 and 2 (ERK1/2) through the formation of β‐arrestin scaffolds. Two such receptors, protease activated receptor‐2 (PAR‐2) and neurokinin 1 receptor (NK1R), promote β‐arrestin‐dependent ERK1/2 activation, but the scaffolding complexes formed differ in their composition, stability, and subcellular localization. While PAR‐2 promotes cytosolic retention of activated ERK1/2 through association with β‐arrestins leading to cell motility, NK1R promotes nuclear translocation of ERK1/2 and proliferation. To examine the possibility that the C‐termini of these two receptors govern their association with β‐arrestins and the ultimate consequences of scaffolding complex formation, we created chimeras in which the N‐terminus of PAR‐2 was fused to the C‐terminus of NK1R and vice versa. Using subcellular fractionation and confocal microscopy to determine ERK1/2 localization, calcium mobilization assays to determine signal duration, and cell migration and proliferation assays, we show that swapping the C‐termini results in a PAR‐2‐like response to NK1R agonists and an NK1R‐like response to PAR‐2 agonists, suggesting that the C‐termini of the receptors are sufficient to direct specific β‐arrestin signaling events.