Activation of the NADPH oxidase involves the small GTP-binding protein p21rac1

Abo, Arie; Pick, Edgar; Hall, Alan; Totty, Nicholas F.; Teahan, Carmel G.; Segal, Anthony W.

doi:10.1038/353668a0

Cited by 918 publications

(586 citation statements)

References 35 publications

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“…P67 phox , one of the essential subunits of NADPH oxidase, is a direct target of Rac1 and Rac2. 22,23 In this way, the activity of these smgs determines the rate and duration of superoxide production. Direct targets of Rho (mDia), Rac (PAK and WAVE) and Cdc42 (WASP) are involved in regulation of actin polymerization, whereas Rho regulates myosin contractility via its direct target Rho kinase (ROCK).…”

Section: How Many Rho Family Gaps Are Involved In Organizing a Funcmentioning

confidence: 99%

The neglected terminators: Rho family GAPs in neutrophils

Csépányi-Kömi

Pásztor

Bartos

et al. 2018

Eur J Clin Investigation

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Background: GTPase-activating proteins (GAPs) accelerate the rate of hydrolysis of GTP bound to small GTPases, thereby limiting the prevalence and concentration of the active, GTP-bound form of these proteins. The large number of potential GAPs acting on members of the Rho family of small GTPases raises the question of specificity or redundancy. Results: In this review, we summarize experimental data obtained on the role of Rho family GAPs in neutrophils, highlight cases where more than one GAP is involved in a physiological function and show examples that GAPs can be involved not only in termination but also in initiation of cellular processes. We demonstrate that the expression-level regulation of GAPs may also occur in shortliving cells such as neutrophils. Finally, we provide insight into the existence and structure of molecular complexes in which Rho family GAPs are involved. Conclusion: GAPs play more complex and varied roles than being simple terminators of cellular processes. K E Y W O R D SGTPase activating proteins, Rho-family small GTPases, neutrophils

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Section: How Many Rho Family Gaps Are Involved In Organizing a Funcmentioning

confidence: 99%

The neglected terminators: Rho family GAPs in neutrophils

Csépányi-Kömi

Pásztor

Bartos

et al. 2018

Eur J Clin Investigation

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“…Pro-apoptotic signal induced by Ras overexpression is overridden by a dominant negative form of Rac1. 24 As Rac1 is a well known component of the NADPH oxydase complex that produces reactive oxygen species (ROS) once activated, 25 reduction of Rac1 activities might also reduce ROS production and favor cell survival. 26 Figure 2.…”

Section: Down-regulation Of Rho Gtpases and Tumorigenesismentioning

confidence: 99%

Inhibition of Cdc42 and Rac1 activities in pheochromocytoma, the adrenal medulla tumor

et al. 2016

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Altered Rho GTPase signaling has been linked to many types of cancer. As many small G proteins, Rho GTPases cycle between an active and inactive state thanks to specific regulators that catalyze exchange of GDP into GTP (Rho-GEF) or hydrolysis of GTP into GDP (Rho-GAP). Recent studies have shown that alteration takes place either at the level of Rho proteins themselves (expression levels, point mutations) or at the level of their regulators, mostly RhoGEFs and RhoGAPs. Most reports describe Rho GTPases gain of function that may participate to the tumorigenesis processes. In contrast, we have recently reported that decreased activities of Cdc42 and Rac1 as well as decreased expression of 2 Rho-GEFs, FARP1 and ARHGEF1, correlate with pheochromocytomas, a tumor developing in the medulla of the adrenal gland (Croise et al., Endocrine Related Cancer, 2016). Here we highlight the major evidence and further study the correlation between Rho GTPases activities and expression levels of ARHGEF1 and FARP1. Finally we also discuss how the decrease of Cdc42 and Rac1 activities may help human pheochromocytomas to develop and comment the possible relationship between FARP1, ARHGEF1 and the 2 Rho GTPases Cdc42 and Rac1 in tumorigenesis.

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“…Published reports show that upon activation of chemoattractant GPCRs, the released G protein βγ subunits triggers PI3K activation and the production of PIP3 [30] . The membranebound PIP3 is required for the subsequent activation of Akt and the small GTPase Rac, which is also required for the assembly of a functional NADPH oxidase complex [31,32] . Thus, chemoattractant-induced ROS production requires simultaneous and sustained activation of multiple signaling pathways, which are also negatively regulated by phosphatases [33] .…”

Section: Superoxide Generationmentioning

confidence: 99%