Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.6.3.1 (NADPH oxidase)
11,281 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Reactive oxygen species (ROS) production by an NADPH oxidase (NOX) encoded by AtrbohC/RHD2 is required for root hair growth in Arabidopsis thaliana. ROP (RHO of plants) GTPases are also required for normal root hair growth and have been proposed to regulate ROS production in plants. Therefore, the role of ROP GTPase in NOX-dependent ROS formation by root hairs was investigated. Plants overexpressing wild-type ROP2 (ROP2 OX), constitutively active (CA-rop2), or dominant negative (DN-rop2) rop2 mutant proteins were used. Superoxide formation by root hairs was detected by superoxide dismutase-sensitive nitroblue tetrazolium reduction, and ROS production in the root hair differentiation zone was detected by dihydrofluorescein diacetate oxidation. Both probes showed that ROS production was increased in ROP2 OX and CA-rop2 plants, and decreased in DN-rop2 plants, relative to wild-type plants. When CA-rop2 was expressed in the NOX loss-of-function rhd2-1 mutant, ROS formation and root hair growth were impaired, suggesting that RHD2 is required for this ROP2-dependent ROS formation.
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PMID:NADPH oxidase-dependent reactive oxygen species formation required for root hair growth depends on ROP GTPase. 1730 Oct 29

Plant RHO GTPases (RAC/ROPs) mediate multiple extracellular signals ranging from hormone to stress and regulate diverse cellular processes important for polarized cell growth, differentiation, development, reproduction, and responses to the environment. They shuttle between the GDP-bound inactive state and the GTP-bound activated state and their activation is predominantly mediated by a family of guanine nucleotide exchange factors (GEFs) referred to as ROPGEFs. Using the Arabidopsis ROPGEF1 as bait, we identified members of a receptor-like kinase (RLK) family as potential upstream regulators for RAC/ROP signaling. NADPH oxidase-derived reactive oxygen species (ROS) are emerging as important regulators for growth and development and play a crucial role in mediating RAC/ROP-regulated root hair development, a polarized cell growth process. We therefore screened T-DNA insertion mutants in these RLKs for root hair defects and found that mutations in one of them, At3g51550 encoding the FERONIA (FER) receptor-like kinase, induced severe root hair defects. We show that the fer phenotypes correlated with reduced levels of active RAC/ROPs and NADPH oxidase-dependent, auxin-regulated ROS accumulation in roots and root hairs and that up-regulating RAC/ROP signaling in fer countered the mutant phenotypes. Taken together, these observations strongly support FER as an upstream regulator for the RAC/ROP-signaled pathway that controls ROS-mediated root hair development. Moreover, FER was pulled down by ROP2 GTPase in a guanine nucleotide-regulated manner implying a dynamic signaling complex involving FER, a ROPGEF, and a RAC/ROP.
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PMID:FERONIA receptor-like kinase regulates RHO GTPase signaling of root hair development. 2092 48

Reactive oxygen species (ROS) play an important role as triggers of gene expression during biotic and abiotic stresses, among which is low oxygen (O(2)). Previous studies have shown that ROS regulation under low O(2) is driven by a RHO-like GTPase that allows tight control of hydrogen peroxide (H(2)O(2)) production. H(2)O(2) is thought to regulate the expression of heat shock proteins, in a mechanism that is common to both O(2) deprivation and to heat stress. In this work, we used publicly available Arabidopsis (Arabidopsis thaliana) microarray datasets related to ROS and O(2) deprivation to define transcriptome convergence pattern. Our results show that although Arabidopsis response to anoxic and hypoxic treatments share a common core of genes related to the anaerobic metabolism, they differ in terms of ROS-related gene response. We propose that H(2)O(2) production under O(2) deprivation is a trait present in a very early phase of anoxia, and that ROS are needed for the regulation of a set of genes belonging to the heat shock protein and ROS-mediated groups. This mechanism, likely not regulated via the N-end rule pathway for O(2) sensing, is probably mediated by a NADPH oxidase and it is involved in plant tolerance to the stress.
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PMID:Reactive oxygen species-driven transcription in Arabidopsis under oxygen deprivation. 2241 14

Transient increases in mitochondrially-derived reactive oxygen species (ROS) activate an adaptive stress response to promote longevity. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases produce ROS locally in response to various stimuli, and thereby regulate many cellular processes, but their role in aging remains unexplored. Here, we identified the C. elegans orthologue of mammalian mediator of ErbB2-driven cell motility, MEMO-1, as a protein that inhibits BLI-3/NADPH oxidase. MEMO-1 is complexed with RHO-1/RhoA/GTPase and loss of memo-1 results in an enhanced interaction of RHO-1 with BLI-3/NADPH oxidase, thereby stimulating ROS production that signal via p38 MAP kinase to the transcription factor SKN-1/NRF1,2,3 to promote stress resistance and longevity. Either loss of memo-1 or increasing BLI-3/NADPH oxidase activity by overexpression is sufficient to increase lifespan. Together, these findings demonstrate that NADPH oxidase-induced redox signaling initiates a transcriptional response that protects the cell and organism, and can promote both stress resistance and longevity.
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PMID:NADPH oxidase-mediated redox signaling promotes oxidative stress resistance and longevity through memo-1 in C. elegans. 2808 66

An accumulating body of evidence suggests that transient or physiological reactive oxygen species (ROS) generated by nicotinamide adenine dinucleotide phosphate (NADPH) oxidases act as a redox signal to re-establish homeostasis. The capacity to re-establish homeostasis progressively declines during aging but is maintained in long-lived animals to promote healthy aging. In the model organism Caenorhabditis elegans, ROS generated by dual oxidases (Duox) are important for extracellular matrix integrity, pathogen defense, oxidative stress resistance, and longevity. The Duox enzymatic activity is tightly regulated and under cellular control. Developmental molting cycles, pathogen infections, toxins, mitochondrial-derived ROS, drugs, and small GTPases (e.g., RHO-1) can activate Duox (BLI-3) to generate ROS, whereas NADPH oxidase inhibitors and negative regulators, such as MEMO-1, can inhibit Duox from generating ROS. Three mechanisms-of-action have been discovered for the Duox/BLI-3-generated ROS: (1) enzymatic activity to catalyze crosslinking of free tyrosine ethyl ester in collagen bundles to stabilize extracellular matrices, (2) high ROS bursts/levels to kill pathogens, and (3) redox signaling activating downstream kinase cascades to transcription factors orchestrating oxidative stress and immunity responses to re-establish homeostasis. Although Duox function at the cell surface is well established, recent genetic and biochemical data also suggests a novel role for Duoxs at the endoplasmic reticulum membrane to control redox signaling. Evidence underlying these mechanisms initiated by ROS from NADPH oxidases, and their relevance for human aging, are discussed in this review. Appropriately controlling NADPH oxidase activity for local and physiological redox signaling to maintain cellular homeostasis might be a therapeutic strategy to promote healthy aging.
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PMID:Redox Signaling of NADPH Oxidases Regulates Oxidative Stress Responses, Immunity and Aging. 3027 29

The RAS-related C3 botulinum toxin substrate 2 (RAC2) is a member of the RHO subclass of RAS superfamily GTPases required for proper immune function. An activating mutation in a key switch II region of RAC2 (RAC2^E62K) involved in recognizing modulatory factors and effectors has been identified in patients with common variable immune deficiency. To better understand how the mutation dysregulates RAC2 function, we evaluated the structure and stability, guanine nucleotide exchange factor (GEF) and GTPase-activating protein (GAP) activity, and effector binding of RAC2^E62K Our findings indicate the E62K mutation does not alter RAC2 structure or stability. However, it does alter GEF specificity, as RAC2^E62K is activated by the DOCK GEF, DOCK2, but not by the Dbl homology GEF, TIAM1, both of which activate the parent protein. Our previous data further showed that the E62K mutation impairs GAP activity for RAC2^E62K As this disease mutation is also found in RAS GTPases, we assessed GAP-stimulated GTP hydrolysis for KRAS and observed a similar impairment, suggesting that the mutation plays a conserved role in GAP activation. We also investigated whether the E62K mutation alters effector binding, as activated RAC2 binds effectors to transmit signaling through effector pathways. We find that RAC2^E62K retains binding to an NADPH oxidase (NOX2) subunit, p67^phox, and to the RAC-binding domain of p21-activated kinase, consistent with our earlier findings. Taken together, our findings indicate that the RAC2^E62K mutation promotes immune dysfunction by promoting RAC2 hyperactivation, altering GEF specificity, and impairing GAP function yet retaining key effector interactions.
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PMID:The molecular basis for immune dysregulation by the hyperactivated E62K mutant of the GTPase RAC2. 3263 2

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