RHO GTPases Activate NADPH Oxidases
NOX2 complex consists of CYBB (NOX2), CYBA (p22phox), NCF1 (p47phox), NCF2 (p67phox) and NCF4 (p40ohox). RAC1:GTP binds NOX2 complex in response to VEGF signaling by directly interracting with CYBB and NCF2, leading to enhancement of VEGF-signaling through VEGF receptor VEGFR2, which plays a role in angiogenesis (Price et al. 2002, Bedard and Krause 2007). RAC2:GTP can also activate the NOX2 complex by binding to CYBB and NCF2, leading to production of superoxide in phagosomes of neutrophils which is necessary fo the microbicidal activity of neutrophils (Knaus et al. 1991, Roberts et al. 1999, Kim and Dinauer 2001, Jyoti et al. 2014).
NOX1 complex (composed of NOX1, NOXA1, NOXO1 and CYBA) and NOX3 complex (composed of NOX3, CYBA, NCF1 amd NCF2 or NOXA1) can also be activated by binding to RAC1:GTP to produce superoxide (Cheng et al. 2006, Miyano et al. 2006, Ueyama et al. 2006).
| UniProt ID | Protein Name | Gene Symbol | Pathway Viewer |
|---|---|---|---|
| P04839 | NADPH oxidase 2 |
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| P15153 | Ras-related C3 botulinum toxin substrate 2 |
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| P17252 | Protein kinase C alpha type |
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| P63000 | Ras-related C3 botulinum toxin substrate 1 |
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| Q99570 | Phosphoinositide 3-kinase regulatory subunit 4 |
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| Q9HBY0 | NADPH oxidase 3 |
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| Q9Y5S8 | NADPH oxidase 1 |
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Supported by JST NBDC Grant Number JPMJND2204
Partly supported by NIH Common Fund Grant #1U01GM125267-01
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