| First Author | Robichaux WG 3rd | Year | 2017 |
| Journal | J Pharmacol Exp Ther | Volume | 360 |
| Issue | 3 | Pages | 424-433 |
| PubMed ID | 28062526 | Mgi Jnum | J:241306 |
| Mgi Id | MGI:5901783 | Doi | 10.1124/jpet.116.238436 |
| Citation | Robichaux WG 3rd, et al. (2017) Regulation of Chemokine Signal Integration by Activator of G-Protein Signaling 4 (AGS4). J Pharmacol Exp Ther 360(3):424-433 |
| abstractText | Activator of G-protein signaling 4 (AGS4)/G-protein signaling modulator 3 (Gpsm3) contains three G-protein regulatory (GPR) motifs, each of which can bind Galphai-GDP free of Gbetagamma We previously demonstrated that the AGS4-Galphai interaction is regulated by seven transmembrane-spanning receptors (7-TMR), which may reflect direct coupling of the GPR-Galphai module to the receptor analogous to canonical Galphabetagamma heterotrimer. We have demonstrated that the AGS4-Galphai complex is regulated by chemokine receptors in an agonist-dependent manner that is receptor-proximal. As an initial approach to investigate the functional role(s) of this regulated interaction in vivo, we analyzed leukocytes, in which AGS4/Gpsm3 is predominantly expressed, from AGS4/Gpsm3-null mice. Loss of AGS4/Gpsm3 resulted in mild but significant neutropenia and leukocytosis. Dendritic cells, T lymphocytes, and neutrophils from AGS4/Gpsm3-null mice also exhibited significant defects in chemoattractant-directed chemotaxis and extracellular signal-regulated kinase activation. An in vivo peritonitis model revealed a dramatic reduction in the ability of AGS4/Gpsm3-null neutrophils to migrate to primary sites of inflammation. Taken together, these data suggest that AGS4/Gpsm3 is required for proper chemokine signal processing in leukocytes and provide further evidence for the importance of the GPR-Galphai module in the regulation of leukocyte function. |
