A potent inhibitor of endothelial cell proliferation is generated by proteolytic cleavage of the chemokine platelet factor 4.

• DOI: 10.1073/pnas.92.17.7799
• Publication Date: 2006-05-31T13:17:17Z
• Authors: S K Gupta; T Hassel; J P Singh
• Keywords: CXC chemokine receptors; Cleavage (geology); CXCL14

Platelet factor 4 (PF-4) is an archetype of the "chemokine" family low molecular weight proteins that play important role in injury responses and inflammation. From activated human leukocyte culture supernatants, we have isolated a form PF-4 acts as potent inhibitor endothelial cell proliferation. The derivative generated by peptide bond cleavage between Thr-16 Ser-17, site located downstream from highly conserved structurally CXC motif. unique leads to loss one large loops molecule generation N terminus with basic residues potential interact acidic extracellular domain G-protein-coupled chemokine receptor. N-terminal processed exhibited 30- 50-fold greater growth inhibitory activity on cells than PF-4. Since inhibition only known cellular cleaved PF-4, designated this inhibitor. processing may represent mechanism for modulating during tissue injury, inflammation, neoplasia.