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Title: 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
Authors: Curcio, Marli F. [UNIFESP]
Batista, Wagner L. [UNIFESP]
Linares, Edlaine [UNIFESP]
Nascimento, Fabio D.
Moraes, Miriam S. [UNIFESP]
Borges, Roberta E. [UNIFESP]
Sap, Jan
Stern, Arnold
Monteiro, Hugo P. [UNIFESP]
Universidade Federal de São Paulo (UNIFESP)
Univ Bandeirante UNIBAN
Univ Copenhagen
Issue Date: 1-Jul-2010
Publisher: Mary Ann Liebert Inc
Citation: Antioxidants & Redox Signaling. New Rochelle: Mary Ann Liebert Inc, v. 13, n. 2, p. 109-125, 2010.
Abstract: 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.
ISSN: 1523-0864
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