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bioRxiv · 10.1101/745596

The putative Gαq-inhibiting pepducin P4Pal10 distinctly modulates function of the Gαi-coupled receptors FPR2 and FFA2R in neutrophils

Holdfeldt, A.·Lind, S.·Dahlgren, C.·Forsman, H.
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Abstract

A novel mechanism of action was described, when a protease-activated receptor 4 (P4Pal10) derived lipopeptide (pepducin) was shown to inhibit signaling downstream of several unrelated Gq-coupled receptors. We show that this putative Gq-inhibiting pepducin lacks inhibitory effects on signaling downstream of the Gq-coupled receptors for ATP (P2Y2R) and PAF (PAFR) expressed in human neutrophils. P4Pal10 inhibited however, signaling in neutrophils activated with agonists for the Gi-coupled formyl peptide receptor 2 (FPR2) but not the closely related FPR1. In addition, the P4Pal10 pepducin was turned into an activating agonist in the presence of an allosteric modulator selective for free fatty acid receptor 2 (FFA2R). The results presented thus reveal Gq-independent effects of P4Pal10 in modulating FPR2- and FFA2R-mediated neutrophil activation.

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Holdfeldt, A., Lind, S., Dahlgren, C., Forsman, H.. 2019-08-23. The putative Gαq-inhibiting pepducin P4Pal10 distinctly modulates function of the Gαi-coupled receptors FPR2 and FFA2R in neutrophils. https://doi.org/10.1101/745596

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