| Autor: |
M'Rabet, Laura, Coffer, P.J., Wolthuis, R.M.F., Zwartkruis, G.J.T., Koenderman, L., Bos, J.L. |
| Jazyk: |
angličtina |
| Rok vydání: |
1999 |
| Předmět: |
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| Zdroj: |
The Journal of Bioligical Chemistry, 274(31), 21847. The American Society for Biochemistry and Molecular Biology, Inc. |
| Popis: |
We have measured the activation of the small GTPase Ral in human neutrophils after stimulation with fMet- Leu-Phe (fMLP), platelet activating factor (PAF), and granulocyte macrophage-colony stimulating factor and compared it with the activation of two other small GTPases, Ras and Rap1. We found that fMLP and PAF, but not granulocyte macrophage-colony stimulating factor, induce Ral activation. All three stimuli induce the activation of both Ras and Rap1. Utilizing specific inhibitors we demonstrate that fMLP-induced Ral activation is mediated by pertussis toxin-sensitive G-proteins and partially by Src-like kinases, whereas fMLP-induced Ras activation is independent of Src-like kinases. PAFinduced Ral activation is mediated by pertussis toxininsensitive proteins, Src-like kinases and phosphatidylinositol 3-kinase. Phosphatidylinositol 3-kinase is not involved in PAF-induced Ras activation. The calcium ionophore ionomycin activates Ral, but calcium depletion partially inhibits fMLP- and PAF-induced Ral activation, whereas Ras activation was not affected. In addition, 12-O-tetradecanoylphorbol-13-acetate-induced activation of Ral is completely abolished by inhibitors of protein kinase C, whereas 12-O-tetradecanoylphorbol- 13-acetate-induced Ras activation is largely insensitive. We conclude that in neutrophils Ral activation is mediated by multiple pathways, and that fMLP and PAF induce Ral activation differently. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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