S. Lind

The ketone body acetoacetate activates human neutrophils through FFA2R

This study shows that acetoacetate activates human neutrophils via FFA2R, affecting cAMP levels, calcium signaling, ROS production, and migration.

THE ALLOSTERICALLY MODULATED FREE FATTY ACID RECEPTOR 2 IS TRANSACTIVATED BY AN INCREASE IN THE CYTOSOLIC CONCENTRATION OF CALCIUM IONS

The paper shows that P2Y2R signals, via Gq and increased [Ca2+]i, transactivate allosterically modulated FFA2R, revealing a unique cross-talk mechanism between GPCRs.

Structural determinants in the Staphylococcus aureus derived phenol-soluble modulin-α2 peptide required for neutrophil formyl peptide receptor activation

This study identifies structural features of PSM2 that determine its selectivity for FPR1 and FPR2 and its biased signaling properties.

Allosteric Receptor Modulation uncovers an FFAR2 antagonist as a positive orthosteric modulator/agonist in disguise

The paper reveals that GLPG0974, previously classified as an FFAR2 antagonist, also acts as a positive orthosteric modulator/agonist by enhancing neutrophil activation and downstream signaling when combined with co-agonistic PAMs.

Multiple ligand recognition sites in free fatty acid receptor 2 (FFAR2) direct distinct neutrophil activation patterns

The paper identifies two distinct allosteric modulators of FFAR2 that trigger different neutrophil activation patterns through separate binding sites.

Functional selective FPR1 signaling in favor of an activation of the neutrophil superoxide generating NOX2-complex

This study identifies a novel FPR1 agonist, RE, that shows biased signaling and functional selectivity in human neutrophils, potentially useful for anti-inflammatory therapeutics.

Interdependent allosteric FFA2R modulators synergistically induce functional selective activation and desensitization in neutrophils

The paper shows two non-activating FFA2R allosteric modulators synergistically activate neutrophil NADPH-oxidase without triggering Ca2+ signaling.

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

The paper shows that P4Pal10, a Gαq-inhibiting pepducin, modulates FPR2 and FFA2R signaling in neutrophils independently of Gq pathways.

Functional and signaling characterization of the neutrophil FPR2 selective agonist Act-389949

This study characterizes Act-389949, a FPR2 agonist, showing it induces neutrophil signaling and chemotaxis comparable to WKYMVM, with increased stability against oxidation.