Ras, Rac1, and phosphatidylinositol-3-kinase (PI3K) signaling in nitric oxide induced endothelial cell migration
| Autor: | Paulo E da Costa, Scheilla Teixeira Strumillo, Adriano Sartori, Arnold Stern, Rita Tokikawa, Murched Omar Taha, Roberta Eller-Borges, Miriam S. Moraes, Hugo P. Monteiro, Graciele Almeida de Oliveira, Fabio V. Fonseca, Marli F. Curcio, Wagner L. Batista |
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| Rok vydání: | 2015 |
| Předmět: |
rac1 GTP-Binding Protein
Cancer Research Physiology Kinase Cellular differentiation Clinical Biochemistry Endothelial Cells RAC1 Cell migration Biology Bradykinin Nitric Oxide Biochemistry Cell biology Endothelial stem cell Phosphatidylinositol 3-Kinases Cell Movement Anti-apoptotic Ras signalling cascade ras Proteins Humans Signal transduction PI3K/AKT/mTOR pathway Signal Transduction |
| Zdroj: | Nitric Oxide. 47:40-51 |
| ISSN: | 1089-8603 |
| Popis: | The small GTP-binding proteins Ras and Rac1 are molecular switches exchanging GDP for GTP and converting external signals in response to a variety of stimuli. Ras and Rac1 play an important role in cell proliferation, cell differentiation, and cell migration. Rac1 is directly involved in the reorganization and changes in the cytoskeleton during cell motility. Nitric oxide (NO) stimulates the Ras – ERK1/2 MAP kinases signaling pathway and is involved in the interaction between Ras and the phosphatidyl-inositol-3 Kinase (PI3K) signaling pathway and cell migration. This study utilizes bradykinin (BK), which promotes endogenous production of NO, in an investigation of the role of NO in the activation of Rac1 in rabbit aortic endothelial cells (RAEC). NO-derived from BK stimulation of RAEC and incubation of the cells with the s-nitrosothiol S-nitrosoglutathione (GSNO) activated Rac1. NO-derived from BK stimulation promoted RAEC migration over a period of 12 h. The use of RAEC permanently transfected with the dominant negative mutant of Ras (Ras N17 ) or with the non-nitrosatable mutant of Ras (Ras C118S ); and the use of specific inhibitors of: Ras, PI3K, and Rac1 resulted in inhibition of NO-mediated Rac1 activation. BK-stimulated s-nitrosylation of Ras in RAEC mediates Rac1 activation and cell migration. Inhibition of NO-mediated Rac1 activation resulted in inhibition of endothelial cell migration. In conclusion, the NO indirect activation of Rac1 involves the direct participation of Ras and PI3K in the migration of endothelial cells stimulated with BK. |
| Databáze: | OpenAIRE |
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