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

Neel NF, Barzik M, Raman D, Sobolik-Delmaire T, Sai J, Ham AJ, Mernaugh RL, Gertler FB, Richmond A
J Cell Sci. 2009 122 (Pt 11): 1882-94

PMID: 19435808 · PMCID: PMC2684839 · DOI:10.1242/jcs.039057

Chemotaxis regulates the recruitment of leukocytes, which is integral for a number of biological processes and is mediated through the interaction of 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 through novel receptor-interacting proteins. CXCR2 is a major chemokine receptor expressed on neutrophils. We used a 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 a CXCR2-interacting protein. The interaction between CXCR2 and VASP is direct and enhanced by CXCL8 stimulation, which triggers VASP phosphorylation via PKA- and PKCdelta-mediated pathways. The interaction between CXCR2 and VASP requires free F-actin barbed ends to recruit VASP to the leading edge. Finally, knockdown of VASP in HL-60 cells results in severely impaired CXCR2-mediated chemotaxis and polarization. These data provide the first demonstration that direct interaction of VASP with CXCR2 is essential for proper CXCR2 function and demonstrate a crucial role for VASP in mediating chemotaxis in leukocytes.

MeSH Terms (20)

Actins Animals Cell Adhesion Molecules Cell Membrane Cell Polarity Chemotaxis Cyclic AMP-Dependent Protein Kinases HL-60 Cells Humans Interleukin-8 Leukocytes Microfilament Proteins Phosphoproteins Phosphorylation Protein Kinase C Protein Structure, Tertiary Receptors, Interleukin-8B Recombinant Fusion Proteins Serine Signal Transduction

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