A Dominant-Negative p65 PAK Peptide Inhibits Angiogenesis
| Autor: | Mary E. Gerritsen, Nazilla B. Alderson, Martin A. Schwartz, John Hood, Suya Yang, David A. Cheresh, William B. Kiosses |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Physiology
Angiogenesis Recombinant Fusion Proteins Neovascularization Physiologic Peptide macromolecular substances CDC42 Protein Serine-Threonine Kinases Biology environment and public health SH3 domain PAK1 Cell Movement Humans Protein kinase A Cells Cultured Adaptor Proteins Signal Transducing Oncogene Proteins chemistry.chemical_classification Signal transducing adaptor protein equipment and supplies Cell biology Endothelial stem cell enzymes and coenzymes (carbohydrates) p21-Activated Kinases chemistry Biochemistry Gene Products tat Mutation Endothelium Vascular biological phenomena cell phenomena and immunity Peptides Cardiology and Cardiovascular Medicine Protein Binding |
| Zdroj: | Circulation Research. 90:697-702 |
| ISSN: | 1524-4571 0009-7330 |
| DOI: | 10.1161/01.res.0000014227.76102.5d |
| Popis: | PAK1 is a protein kinase downstream of the small GTPases Rac and Cdc42 that previous work has implicated in endothelial cell migration via modulation of cell contraction. The first proline-rich region of PAK that binds to an SH3 domain from the adapter protein NCK was responsible for these dominant-negative effects. To test the role of PAK in angiogenesis, we prepared a peptide in which the proline-rich region was fused to the polybasic sequence from the HIV Tat protein to facilitate entry into cells. We show that the short peptide selectively binds NCK, whereas a mutant peptide does not. Treatment of cells with the PAK peptide but not the control peptide disrupts localization of PAK. This peptide specifically inhibited endothelial cell migration and contractility similarly to full-length dominant-negative PAK. In an in vitro tube-forming assay, the PAK peptide specifically blocked formation of multicellular networks. In an in vivo chick chorioallantoic membrane assay, the PAK peptide specifically blocked angiogenesis. These results, therefore, suggest a role for PAK in angiogenesis. |
| Databáze: | OpenAIRE |
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