Co-regulation of constitutive nitric oxide synthases and NADPH oxidase by the small GTPase Rac

Balakrishnan Selvakumar; Douglas T. Hess; Pascal J. Goldschmidt-Clermont; Jonathan S. Stamler

doi:10.1016/j.febslet.2008.04.062

Co-regulation of constitutive nitric oxide synthases and NADPH oxidase by the small GTPase Rac

Balakrishnan Selvakumar, Douglas T. Hess, Pascal J. Goldschmidt-Clermont, Jonathan S. Stamler

Medicine

Research output: Contribution to journal › Article › peer-review

35 Scopus citations

Abstract

Nitric oxide (NO), generated by NO synthases (NOSs), has multifarious roles in signal transduction. Reactive oxygen species (ROS), generated by ubiquitous NADPH oxidases (NOXs), also participate in cellular signaling. However, the coordination of signals conveyed by NO and ROS is poorly understood. We show that the small GTPase Rac, a component of some NOXs, also interacts with and regulates the constitutively-expressed NOSs. Cellular NO and O₂^- production increase or decrease together following activation or inhibition of Rac, and Rac inhibition reveals transduction mechanisms that depend upon NO (vasodilation), ROS (actin polymerization) or both (cytoskeletal organization). Thus, signaling by NO and ROS may be coordinated through a common control element.

Original language	English (US)
Pages (from-to)	2195-2202
Number of pages	8
Journal	FEBS letters
Volume	582
Issue number	15
DOIs	https://doi.org/10.1016/j.febslet.2008.04.062
State	Published - Jun 25 2008

Keywords

NADPH oxidase
Nitric oxide
Nitric oxide synthase
Rac
Small GTPase

ASJC Scopus subject areas

Biochemistry
Biophysics
Molecular Biology

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title = "Co-regulation of constitutive nitric oxide synthases and NADPH oxidase by the small GTPase Rac",

abstract = "Nitric oxide (NO), generated by NO synthases (NOSs), has multifarious roles in signal transduction. Reactive oxygen species (ROS), generated by ubiquitous NADPH oxidases (NOXs), also participate in cellular signaling. However, the coordination of signals conveyed by NO and ROS is poorly understood. We show that the small GTPase Rac, a component of some NOXs, also interacts with and regulates the constitutively-expressed NOSs. Cellular NO and O2- production increase or decrease together following activation or inhibition of Rac, and Rac inhibition reveals transduction mechanisms that depend upon NO (vasodilation), ROS (actin polymerization) or both (cytoskeletal organization). Thus, signaling by NO and ROS may be coordinated through a common control element.",

keywords = "NADPH oxidase, Nitric oxide, Nitric oxide synthase, Rac, Small GTPase",

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T1 - Co-regulation of constitutive nitric oxide synthases and NADPH oxidase by the small GTPase Rac

AU - Selvakumar, Balakrishnan

AU - Hess, Douglas T.

AU - Goldschmidt-Clermont, Pascal J.

AU - Stamler, Jonathan S.

PY - 2008/6/25

Y1 - 2008/6/25

N2 - Nitric oxide (NO), generated by NO synthases (NOSs), has multifarious roles in signal transduction. Reactive oxygen species (ROS), generated by ubiquitous NADPH oxidases (NOXs), also participate in cellular signaling. However, the coordination of signals conveyed by NO and ROS is poorly understood. We show that the small GTPase Rac, a component of some NOXs, also interacts with and regulates the constitutively-expressed NOSs. Cellular NO and O2- production increase or decrease together following activation or inhibition of Rac, and Rac inhibition reveals transduction mechanisms that depend upon NO (vasodilation), ROS (actin polymerization) or both (cytoskeletal organization). Thus, signaling by NO and ROS may be coordinated through a common control element.

AB - Nitric oxide (NO), generated by NO synthases (NOSs), has multifarious roles in signal transduction. Reactive oxygen species (ROS), generated by ubiquitous NADPH oxidases (NOXs), also participate in cellular signaling. However, the coordination of signals conveyed by NO and ROS is poorly understood. We show that the small GTPase Rac, a component of some NOXs, also interacts with and regulates the constitutively-expressed NOSs. Cellular NO and O2- production increase or decrease together following activation or inhibition of Rac, and Rac inhibition reveals transduction mechanisms that depend upon NO (vasodilation), ROS (actin polymerization) or both (cytoskeletal organization). Thus, signaling by NO and ROS may be coordinated through a common control element.

KW - NADPH oxidase

KW - Nitric oxide

KW - Nitric oxide synthase

KW - Rac

KW - Small GTPase

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