Functional and structural consequences of chemokine (C-X-C motif) receptor 4 activation with cognate and non-cognate agonists.

摘要: Chemokine (C-X-C motif) receptor 4 (CXCR4) regulates cell trafficking and plays important roles in the immune system. Ubiquitin has recently been identified as an endogenous non-cognate agonist of CXCR4, which activates CXCR4 via interaction sites that are distinct from those cognate C-X-C motif chemokine ligand 12 (CXCL12). As compared with CXCL12, chemotactic activities ubiquitin primary human cells poorly characterized. Furthermore, evidence for functional selectivity agonists is lacking, structural consequences binding to unknown. Here, we show CXCL12 have comparable normal peripheral blood mononuclear cells, monocytes, vascular smooth muscle, endothelial cells. Chemotactic ligands could be inhibited selective antagonist AMD3100 a peptide analogue second transmembrane domain CXCR4. In ubiquitin- CXCL12-induced chemotaxis pertussis toxin inhibitors phospholipase C, phosphatidylinositol 3 kinase, extracellular signal-regulated kinase 1/2. Both induced inositol trisphosphate production muscle AMD3100. β-arrestin recruitment assays, did not sufficiently recruit β-arrestin2 (EC50 > 10 μM), whereas EC50 was 4.6 nM (95% confidence interval 3.1–6.1 nM). similar chemical shift changes 13C-1H-heteronuclear single quantum correlation (HSQC) spectrum membranes, CXCL11 significantly alter 13C-1H-HSQC Our findings point towards biased