| First Author | Cronshaw DG | Year | 2010 |
| Journal | PLoS One | Volume | 5 |
| Issue | 11 | Pages | e15397 |
| PubMed ID | 21124917 | Mgi Jnum | J:167314 |
| Mgi Id | MGI:4867790 | Doi | 10.1371/journal.pone.0015397 |
| Citation | Cronshaw DG, et al. (2010) An essential role of the cytoplasmic tail of CXCR4 in g-protein signaling and organogenesis. PLoS One 5(11):e15397 |
| abstractText | CXCR4 regulates cell proliferation, enhances cell survival and induces chemotaxis, yet molecular mechanisms underlying its signaling remain elusive. Like all other G-protein coupled receptors (GPCRs), CXCR4 delivers signals through G-protein-dependent and -independent pathways, the latter involving its serine-rich cytoplasmic tail. To evaluate the signaling and biological contribution of this G-protein-independent pathway, we generated mutant mice that express cytoplasmic tail-truncated CXCR4 (DeltaT) by a gene knock-in approach. We found that DeltaT mice exhibited multiple developmental defects, with not only G-protein-independent but also G-protein-dependent signaling events completely abolished, despite DeltaT's ability to still associate with G-proteins. These results reveal an essential positive regulatory role of the cytoplasmic tail in CXCR4 signaling and suggest the tail is crucial for mediating G-protein activation and initiating crosstalk between G-protein-dependent and G-protein-independent pathways for correct GPCR signaling. |
