Regulatory Effects of Nitric Oxide on Src Kinase, FAK, p130Cas, and Receptor Protein Tyrosine Phosphatase Alpha (PTP-alpha): A Role for the Cellular Redox Environment

Autor(es)

Curcio, Marli F. ^[1] ; Batista, Wagner L. ^[2] ; Linares, Edlaine ^[3] ; Nascimento, Fabio D. ^[4] ; Moraes, Miriam S. ^[1] ; Borges, Roberta E. ^[1] ; Sap, Jan ^[5] ; Stern, Arnold ^[6] ; Monteiro, Hugo P. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Dept Biochem Mol Biol, CINTERGEN, BR-04044020 Sao Paulo - Brazil

^[2] Univ Fed Sao Paulo, Dept Biol Sci, BR-04044020 Sao Paulo - Brazil

^[3] Univ Fed Sao Paulo, Inst Quim, Dept Biochem, BR-04044020 Sao Paulo - Brazil

^[4] Univ Bandeirante UNIBAN, Grp Study Dent, Sao Paulo - Brazil

^[5] Univ Copenhagen, Dept Pathol, Copenhagen - Denmark

^[6] NYU, Sch Med, Dept Pharmacol, New York, NY - USA

• Tipo de documento: Artigo Científico
• Fonte: Antioxidants & Redox Signaling; v. 13, n. 2, p. 109-125, JUL 2010.
• Citações Web of Science: 19

Resumo

The role of NO in regulating the focal adhesion proteins, Src, FAK, p130 Cas, and PTP-alpha, was investigated. Fibroblasts expressing PTP-alpha (PTP-alpha(WT) cells), fibroblasts ``knockout'' for PTP-alpha (PTP-alpha(-/-) cells), and ``rescued'' ``knockout'' fibroblasts (PTP-alpha A5/3 cells) were stimulated with either S-nitroso-N-acetylpenicillamine (SNAP) or fetal bovine serum (FBS). FBS increased inducible NO synthase in both cell lines. Activation of Src mediated either by SNAP or by FBS occurred independent of dephosphorylation of Tyr527 in PTP-alpha(-/-) cells. Both stimuli promoted dephosphorylation of Tyr527 and activation of Src kinase in PTP-alpha(WT) cells. NO-mediated activation of Src kinase affected the activities of FAK and p130Cas and was dependent on the expression of PTP-alpha. Analogous to tyrosine phosphorylation, SNAP and FBS stimulated differential generation of NO and S-nitrosylation of Src kinase in both cell lines. Incubation with SNAP resulted in higher levels of NO and S-nitrosylation of immunoprecipitated Src in PTP-alpha(-/-) cells (oxidizing redox environment) as compared with the levels of NO and S-nitrosylated Src in PTP-alpha(WT) cells (reducing redox environment). SNAP differentially stimulated cell proliferation of both cell lines is dependent on the intracellular redox environment, Src activity, and PTP-alpha expression. This dependence also is observed with FBS-stimulated cell migration. Antioxid. Redox Signal. 13, 109-125. (AU)

• Processo FAPESP: 06/56311-0 - Estudo dos efeitos do óxido nítrico sobre a atividade sinalizadora de Src quinase em linhagens celulares que expressam ou não a proteína tirosina fosfatase alfa (PTPalfa)
• Beneficiário: Hugo Pequeno Monteiro
• Modalidade de apoio: Auxílio à Pesquisa - Regular