PR-39, a syndecan-inducing antimicrobial peptide, binds and affects p130(Cas).
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.
Chan
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Department of Dermatology and Division of Developmental and Newborn Medicine, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Gallo
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D016475:3T3 Cells; D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism*; D023181:Antimicrobial Cationic Peptides; D050719:Crk-Associated Substrate Protein; D015870:Gene Expression / Q000502:physiology; D008051:Lipid Bilayers; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D008564:Membrane Potentials; D051379:Mice; D010455:Peptides / Q000378:metabolism* / Q000502:physiology; D010750:Phosphoproteins / Q000378:metabolism*; D011485:Protein Binding; D011506:Proteins; D011509:Proteoglycans / Q000096:biosynthesis*; D011994:Recombinant Proteins / Q000378:metabolism; D050717:Retinoblastoma-Like Protein p130; D015398:Signal Transduction / Q000502:physiology; D013347:Subcellular Fractions / Q000378:metabolism; D053667:Syndecans; D018909:src Homology Domains
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; C493842:Bcar1 protein, mouse; D050719:Crk-Associated Substrate Protein; D008051:Lipid Bilayers; D008562:Membrane Glycoproteins; D010455:Peptides; D010750:Phosphoproteins; D011506:Proteins; D011509:Proteoglycans; D011994:Recombinant Proteins; D050717:Retinoblastoma-Like Protein p130; D053667:Syndecans; C072212:PR 39