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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Ras, Rac1, and phosphatidylinositol-3-kinase (PI3K) signaling in nitric oxide induced endothelial cell migration

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Eller-Borges, Roberta [1] ; Batista, Wagner L. [2] ; da Costa, Paulo E. [1] ; Tokikawa, Rita [1] ; Curcio, Marli F. [1] ; Strumillo, Scheilla T. [1] ; Sartori, Adriano [1] ; Moraes, Miriam S. [1] ; de Oliveira, Graciele A. [1] ; Taha, Murched O. [3] ; Fonseca, Fabio V. [4] ; Stern, Arnold [5, 6] ; Monteiro, Hugo P. [1]
Total Authors: 13
[1] Univ Fed Sao Paulo, Escola Paulista Med, Ctr Cellular & Mol Therapy CTCMOL, Dept Biochem, BR-04044010 Sao Paulo, SP - Brazil
[2] Univ Fed Sao Paulo, Dept Biol Sci, Sao Paulo, SP - Brazil
[3] Univ Fed Sao Paulo, Escola Paulista Med, Dept Surg, Sao Paulo, SP - Brazil
[4] Case Western Univ, Inst Transformat Mol Med, Dept Med, Cleveland, OH - USA
[5] NYU, Sch Med, Dept Biochem & Mol Pharmacol, New York, NY - USA
[6] Univ Espiritu Santo, Escuela Med, Guayaquil - Ecuador
Total Affiliations: 6
Document type: Journal article
Source: NITRIC OXIDE-BIOLOGY AND CHEMISTRY; v. 47, p. 40-51, MAY 1 2015.
Web of Science Citations: 10

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. (C) 2015 Elsevier Inc. All rights reserved. (AU)

FAPESP's process: 10/19013-7 - Participation of nitric oxide and Src kinase in the estrogen-stimulated cell signaling pathway in human mammary tumor cells
Grantee:Hugo Pequeno Monteiro
Support type: Regular Research Grants
FAPESP's process: 11/14392-2 - Evaluation of the involvement of Ras GTPase from Paracoccidioides brasiliensis in thermo-dimorphism and during oxidative and nitrosative stress
Grantee:Wagner Luiz Batista
Support type: Regular Research Grants