PR-39, a syndecan-inducing antimicrobial peptide, binds and affects p130Cas

PR-39 is a proline-arginine-rich antimicrobial peptide and an important component of innate immunity, In addition to its antimicrobial effects, PR-39 can alter mammalian cell gene expression and behavior. To determine the mechanism through which PR-39 affects mesenchymal cells, we identify a number of binding targets for PR-39 using a biologically active fragment of PR-39 (PR-39(15)), We found that PR-39 binds NIH 3T3 in a saturable manner consistent with the existence of a binding target. Similar to full-length PR-39, PR-39(15) interacts with lipid bilayers, After interacting with the membrane, PR-39(15) rapidly enters human microvascular endothelial cells and binds a number of cytoplasmic proteins, PR-39 selectively binds recombinant SH3-containing proteins and was also found to bind a native SH3-containing protein, p130(Cas). PR-39(15) treatment of endothelial cells results in altered p130 localization, These results show that PR-39(15) binds an SH3-containing signal transduction molecule that has the potential to explain a myriad of effects PR-39 has on mammalian cell behaviors.