VASP is a CXCR2-interacting protein that regulates CXCR2-mediated polarization and chemotaxis

• DOI: 10.1242/jcs.039057
• Publication Date: 2009-05-13T02:14:42Z
• Authors: Nicole F. Neel; Melanie Barzik; Dayanidhi Raman; Tammy Sobolik-Del...; Jiqing Sai; Amy J. Ham; Raymond L. Mernaugh; Frank B. Gertler; Ann Richmond
• Keywords: CXC chemokine receptors

Chemotaxis regulates the recruitment of leukocytes, which is integral for a number biological processes and mediated through interaction chemokines with seven transmembrane G-protein-coupled receptors. Several studies have indicated that chemotactic signaling pathways might be activated via G-protein-independent mechanisms, perhaps novel receptor-interacting proteins. CXCR2 major chemokine receptor expressed on neutrophils. We used proteomics approach to identify unique ligand-dependent CXCR2-interacting proteins in differentiated neutrophil-like HL-60 cells. Using this approach, vasodilator-stimulated phosphoprotein (VASP) was identified as protein. The between VASP direct enhanced by CXCL8 stimulation, triggers phosphorylation PKA- PKCδ-mediated pathways. requires free F-actin barbed ends recruit leading edge. Finally, knockdown cells results severely impaired CXCR2-mediated chemotaxis polarization. These data provide first demonstration essential proper function demonstrate crucial role mediating leukocytes.