Characterization of the Effector-specifying Domain of Rac Involved in NADPH Oxidase Activation

Kwong, Cheung H.; Adams, Anthony G.; Leto, Thomas L.

doi:10.1074/jbc.270.34.19868

Cited by 76Protein Kinase Regulation and GTPase SignalingNeutrophil, Myeloperoxidase and Oxidative MechanismsRedox biology and oxidative stress

Characterization of the Effector-specifying Domain of Rac Involved in NADPH Oxidase Activation

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Kwong, Cheung H., Adams, Anthony G., Leto, Thomas L.·1995·Journal of Biological Chemistry

DOI 10.1074/jbc.270.34.19868

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Abstract

Production of microbicidal oxidants by phagocytic leukocytes requires activation of a latent NADPH oxidase by the coordinated assembly of a membrane-associated flavocytochrome b558, with three cytosolic components, p47phox, p67phox, and the low molecular weight GTP-binding protein Rac. Rac1 and Rac2 have 92% sequence identity and are both active in supporting the oxidase, while CDC42Hs, the closest relative to Rac with 70% sequence identity, only weakly supports oxidase activation in vitro. We have used CDC42Hs as a foil to identify residues in Rac that are critical for oxidase activation. Most of the divergent sequences of CDC42Hs could be incorporated into Rac-CDC42Hs chimeric proteins without affecting cell-free NADPH oxidase activity. However, incorporation of the amino-terminal segment of CDC42Hs (residues 1-40), which differs from Rac1 by only four residues (positions 3, 27, 30, and 33), resulted in a marked loss of oxidase activation capacity. Point mutagenesis studies showed that this was due to changes at residues 27 and 30, but not residues 3 and 33. Conversely, incorporation of the amino terminus of Rac1 (residues 1-40) into CDC42Hs increased its activity to that of Rac1, indicating that this terminus contains the effector-specifying domain of Rac. Taken together, these studies show that the difference in the activity between CDC42Hs and Rac1 is due entirely to differences in amino acids at position 27 and 30.

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Previous structural and biochemical studies indicated that divergent amino acids at positions 27 and 30 in the switch 1 region of Rac are important for specific recognition and recruitment of its downstream effector p67phox.
“Moreover, previous structural and biochemical studies indicated that divergent amino acids at positions 27 and 30 in the switch 1 region of Rac are important for specific recognition and recruitment of its downstream effector p67 phox , a component of the NADPH oxidase (49,50).”
From Specific Recognition of Rac2 and Cdc42 by DOCK2 and DOCK9 Guanine Nucleotide Exchange Factors (2008) · cites this paper as [49]
p67phox is not a downstream effector of wildtype Cdc42, but Cdc42-to-Rac substitutions at positions 27 and 30 (K27A and S30G) in Cdc42 allow p67phox to serve as an effector of the resulting mutant Cdc42.
“p67 phox is not a downstream effector of wildtype Cdc42, however, Cdc42-to-Rac substitutions at positions 27 and 30 (K27A and S30G) in Cdc42 allows p67 phox to serve as an effector of the resulting mutant Cdc42 (49,50).”
From Specific Recognition of Rac2 and Cdc42 by DOCK2 and DOCK9 Guanine Nucleotide Exchange Factors (2008) · cites this paper as [49]

The small GTP-binding protein rac regulates growth factor-induced membrane ruffling
Ridley, A. J., Paterson, H. F., Johnston, C. L., Diekmann, D., & Hall, A. (1992) · Cell · doi:10.1016/0092-8674(92)90164-8 · Cited by 3,651 · see citing works
Engineering hybrid genes without the use of restriction enzymes: gene splicing by overlap extension
Horton, R. M., Hunt, H. D., Ho, S. N., Pullen, J. K., & Pease, L. R. (1989) · Gene · doi:10.1016/0378-1119(89)90359-4 · Cited by 3,020 · see citing works
A brain serine/threonine protein kinase activated by Cdc42 and Rac1
Manser, E. J., Leung, T., Salihuddin, H., Zhao, Z.-S., & Lim, L. (1994) · Nature · doi:10.1038/367040a0 · Cited by 1,541 · see citing works
Molecular Switch for Signal Transduction: Structural Differences Between Active and Inactive Forms of Protooncogenic ras Proteins
Milburn, M. V., Tong, L., deVos, A. M., Brünger, A. T., Yamaizumi, Z., Nishimura, S., & Kim, S. (1990) · Science · doi:10.1126/science.2406906 · Cited by 1,062 · see citing works
Activation of the NADPH oxidase involves the small GTP-binding protein p21rac1
Abo, A., Pick, E., Hall, A., Totty, N. F., Teahan, C. G., & Segal, A. W. (1991) · Nature · doi:10.1038/353668a0 · Cited by 954 · see citing works
Direct interaction of Ras and the amino-terminal region of Raf-1 in vitro
Warne, P. H., Vician, P. R., & Downward, J. (1993) · Nature · doi:10.1038/364352a0 · Cited by 729 · see citing works
Regulation of Phagocyte Oxygen Radical Production by the GTP-Binding Protein Rac 2
Knaus, U. G., Heyworth, P. G., Evans, T., Curnutte, J. T., & Bokoch, G. (1991) · Science · doi:10.1126/science.1660188 · Cited by 673 · see citing works
Molecular characterization of CDC42, a Saccharomyces cerevisiae gene involved in the development of cell polarity.
Johnson, D. I., & Pringle, J. R. (1990) · The Journal of Cell Biology · doi:10.1083/jcb.111.1.143 · Cited by 543 · see citing works
Two cytosolic components of the human neutrophil respiratory burst oxidase translocate to the plasma membrane during cell activation.
Clark, R. A., Volpp, B. D., Leidal, K. G., & Nauseef, W. M. (1990) · Journal of Clinical Investigation · doi:10.1172/jci114496 · Cited by 431 · see citing works
Two cytosolic neutrophil oxidase components absent in autosomal chronic granulomatous disease
Volpp, B. D., Nauseef, W. M., & Clark, R. A. (1988) · Science · doi:10.1126/science.2848318 · Cited by 407 · see citing works
Cloning of a 67-kD Neutrophil Oxidase Factor with Similarity to a Noncatalytic Region of p60 <sup> <i>c-src</i> </sup>
Leto, T. L., Lomax, K. J., Volpp, B. D., Nunoi, H., Sechler, J. M. G., Nauseef, W. M., Clark, R. A., Gallin, J. I., & Malech, H. L. (1990) · Science · doi:10.1126/science.1692159 · Cited by 386 · see citing works
Self-citation
Interaction of Rac with p67 phox and Regulation pf Phagocytic NADPH Oxidase Activity
Diekmann, D., Abo, A., Johnston, C. L., Segal, A. W., & Hall, A. (1994) · Science · doi:10.1126/science.8036496 · Cited by 382 · see citing works
Cytochrome b 558 : the Flavin-Binding Component of the Phagocyte NADPH Oxidase
Rotrosen, D., Yeung, C. L., Leto, T. L., Malech, H. L., & Kwong, C. H. (1992) · Science · doi:10.1126/science.1318579 · Cited by 378 · see citing works
Self-citation
Neutrophil nicotinamide adenine dinucleotide phosphate oxidase assembly. Translocation of p47-phox and p67-phox requires interaction between p47-phox and cytochrome b558.
Heyworth, P. G., Curnutte, J. T., Nauseef, W. M., Volpp, B. D., Pearson, D. W., Rosen, H., & Clark, R. A. (1991) · Journal of Clinical Investigation · doi:10.1172/jci114993 · Cited by 373 · see citing works
Cytochrome b-245 is a flavocytochrome containing FAD and the NADPH-binding site of the microbicidal oxidase of phagocytes
Segal, A. W., West, I., Wientjes, F. B., Nugent, J. H. A., Chavan, A. J., Haley, B. E., Garcia, R. C., Rosen, H., & Scrace, G. (1992) · Biochemical Journal · doi:10.1042/bj2840781 · Cited by 347 · see citing works
Recombinant 47-Kilodalton Cytosol Factor Restores NADPH Oxidase in Chronic Granulomatous Disease
Lomax, K. J., Leto, T. L., Nunoi, H., Gallin, J. I., & Malech, H. L. (1989) · Science · doi:10.1126/science.2547247 · Cited by 332 · see citing works
Self-citation
Two Forms of Autosomal Chronic Granulomatous Disease Lack Distinct Neutrophil Cytosol Factors
Nunoi, H., Rotrosen, D., Gallin, J. I., & Malech, H. L. (1988) · Science · doi:10.1126/science.2848319 · Cited by 331 · see citing works
Cloning of the cDNA and functional expression of the 47-kilodalton cytosolic component of human neutrophil respiratory burst oxidase.
Volpp, B. D., Nauseef, W. M., Donelson, J. E., Moser, D. J., & Clark, R. A. (1989) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.86.18.7195 · Cited by 305 · see citing works
Reconstitution of neutrophil NADPH oxidase activity in the cell-free system by four components: p67-phox, p47-phox, p21rac1, and cytochrome b-245.
Abo, A., Boyhan, A., West, I., Thrasher, A. J., & Segal, A. W. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)41846-7 · Cited by 267 · see citing works
Rac translocates independently of the neutrophil NADPH oxidase components p47phox and p67phox. Evidence for its interaction with flavocytochrome b558.
Heyworth, P. G., Bohl, B. P., Bokoch, G., & Curnutte, J. T. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)47341-3 · Cited by 263 · see citing works
rho family GTPase activating proteins p190, bcr and rhoGAP show distinct specificities in vitro and in vivo
Ridley, A. J., Self, A. J., Kasmi, F., Paterson, H. F., Hall, A., Marshall, C. J., & Ellis, C. (1993) · The EMBO Journal · doi:10.1002/j.1460-2075.1993.tb06210.x · Cited by 238 · see citing works
The Human Neutrophil Respiratory Burst Oxidase
Clark, R. A. (1990) · The Journal of Infectious Diseases · doi:10.1093/infdis/161.6.1140 · Cited by 222 · see citing works
Carboxyl Methylation of Ras-Related Proteins During Signal Transduction in Neutrophils
Philips, M. R., Pillinger, M. H., Staud, R. M., Volker, C., Rosenfeld, M. G., Weissmann, G., & Stock, J. B. (1993) · Science · doi:10.1126/science.8438158 · Cited by 214 · see citing works
Molecular cloning of the gene for the human placental GTP-binding protein Gp (G25K): identification of this GTP-binding protein as the human homolog of the yeast cell-division-cycle protein CDC42.
Shinjo, K., Koland, J. G., Hart, M. J., Narasimhan, V., Johnson, D. I., Evans, T., & Cerione, R. A. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.24.9853 · Cited by 200 · see citing works
Increased neutrophil respiratory burst in bcr-null mutants
Voncken, J. W., van Schaick, H., Kaartinen, V., Deemer, K., Coates, T. D., Landing, B. H., Pattengale, P. K., Dorseuil, O., Bokoch, G., Groffen, J., et al. (1995) · Cell · doi:10.1016/0092-8674(95)90350-x · Cited by 196 · see citing works
Activation of NADPH oxidase involves the dissociation of p21rac from its inhibitory GDP/GTP exchange protein (rhoGDI) followed by its translocation to the plasma membrane
Abo, A., Webb, M. R., Grogan, A., & Segal, A. W. (1994) · Biochemical Journal · doi:10.1042/bj2980585 · Cited by 181 · see citing works
Regulation of the superoxide-generating NADPH oxidase by a small GTP-binding protein and its stimulatory and inhibitory GDP/GTP exchange proteins.
Mizuno, T., Kaibuchi, K., Ando, S., Musha, T., Hiraoka, K., Takaishi, K., Asada, M., Nunoi, H., Matsuda, I., & Takai, Y. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)50005-9 · Cited by 159 · see citing works
Post-translational processing of rac p21s is important both for their interaction with the GDP/GTP exchange proteins and for their activation of NADPH oxidase.
Ando, S., Kaibuchi, K., Sasaki, T., Hiraoka, K., Nishiyama, T., Mizuno, T., Asada, M., Nunoi, H., Matsuda, I., & Matsuura, Y. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)35665-5 · Cited by 145 · see citing works
Requirement for posttranslational processing of Rac GTP-binding proteins for activation of human neutrophil NADPH oxidase.
Heyworth, P. G., Knaus, U. G., Xu, X., Uhlinger, D. J., Conroy, L., Bokoch, G., & Curnutte, J. T. (1993) · Molecular Biology of the Cell · doi:10.1091/mbc.4.3.261 · Cited by 128 · see citing works
Characterization of neutrophil NADPH oxidase factors p47-phox and p67-phox from recombinant baculoviruses.
Leto, T. L., Garrett, M. C., Fujii, H., & Nunoi, H. (1991) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)55064-x · Cited by 120 · see citing works
Self-citation
Inhibition of superoxide production in B lymphocytes by rac antisense oligonucleotides.
Dorseuil, O., Vázquez, A., Lang, P., Bertoglio, J. H., Gâcon, G., & Leca, G. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)36716-x · Cited by 118 · see citing works
Regulation of the human neutrophil NADPH oxidase by rho-related G-proteins
Kwong, C. H., Malech, H. L., Rotrosen, D., & Leto, T. L. (1993) · Biochemistry · doi:10.1021/bi00072a029 · Cited by 111 · see citing works
Self-citation
Identification of Small Clusters of Divergent Amino Acids that Mediate the Opposing Effects of ras and K rev -1
Zhang, K., Noda, M., Vass, W. C., Papageorge, A. G., & Lowy, D. R. (1990) · Science · doi:10.1126/science.2115210 · Cited by 111 · see citing works
Function of wild-type or mutant Rac2 and Rap1a GTPases in differentiated HL60 cell NADPH oxidase activation
Gabig, T. G., Crean, C., Mantel, P. L., & Rosli, R. (1995) · Blood · doi:10.1182/blood.v85.3.804.bloodjournal853804 · Cited by 109 · see citing works
The membrane-associated component of the amphiphile-activated, cytosol-dependent superoxide-forming NADPH oxidase of macrophages is identical to cytochrome b559.
Knoller, S., Shpungin, S., & Pick, E. (1991) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)49917-6 · Cited by 106 · see citing works
The Cytosolic Activating Factors p47phox and p67phox Have Distinct Roles in the Regulation of Electron Flow in NADPH Oxidase
Cross, A. R., & Curnutte, J. T. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.12.6543 · Cited by 106 · see citing works
Generation of Superoxide by purified and relipidated cytochrome b559 in the absence of cytosolic activators
Koshkin, V., & Pick, E. (1993) · FEBS Letters · doi:10.1016/0014-5793(93)81039-3 · Cited by 94 · see citing works
Regulation of NADPH oxidase activity by Rac GTPase activating protein(s).
Heyworth, P. G., Knaus, U. G., Settleman, J. E., Curnutte, J. T., & Bokoch, G. (1993) · Molecular Biology of the Cell · doi:10.1091/mbc.4.11.1217 · Cited by 93 · see citing works
Differing structural requirements for GTPase-activating protein responsiveness and NADPH oxidase activation by Rac.
Xu, X., Barry, D. C., Settleman, J. E., Schwartz, M. A., & Bokoch, G. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)31553-3 · Cited by 92 · see citing works
Participation of the small molecular weight GTP-binding protein Rac1 in cell-free activation and assembly of the respiratory burst oxidase. Inhibition by a carboxyl-terminal Rac peptide.
Kreck, M. L., Uhlinger, D. J., Tyagi, S. R., Inge, K. L., & Lambeth, J. D. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)41757-1 · Cited by 89 · see citing works
A phosphoprotein of Mr 47,000, defective in autosomal chronic granulomatous disease, copurifies with one of two soluble components required for NADPH:O2 oxidoreductase activity in human neutrophils.
Bolscher, B. G. J. M., van Zwieten, R., Kramer, I. M., Weening, R. S., Verhoeven, A. J., & Roos, D. (1989) · Journal of Clinical Investigation · doi:10.1172/jci113954 · Cited by 85 · see citing works
Different structural organization of Ras and Rho effector domains.
Self, A. J., Paterson, H. F., & Hall, A. (1993) · PubMed · Cited by 84 · see citing works

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Genetic, Biochemical, and Clinical Features of Chronic Granulomatous Disease
Segal, B. H., Leto, T. L., Gallin, J. I., Malech, H. L., & Holland, S. M. (2000) · Medicine · doi:10.1097/00005792-200005000-00004 · Cited by 877 · see citing works
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DeLeo, F. R., & Quinn, M. T. (1996) · Journal of Leukocyte Biology · doi:10.1002/jlb.60.6.677 · Cited by 526 · see citing works
Regulation of NADPH Oxidases
Hordijk, P. L. (2006) · Circulation Research · doi:10.1161/01.res.0000204727.46710.5e · Cited by 525 · see citing works
Assembly of the phagocyte NADPH oxidase
Nauseef, W. M. (2004) · Histochemistry and Cell Biology · doi:10.1007/s00418-004-0679-8 · Cited by 427 · see citing works
Structural organization of the neutrophil NADPH oxidase: phosphorylation and translocation during priming and activation
Sheppard, F. R., Kelher, M. R., Moore, E. E., McLaughlin, N. J. D., Banerjee, A. M., & Silliman, C. C. (2005) · Journal of Leukocyte Biology · doi:10.1189/jlb.0804442 · Cited by 374 · see citing works
Structure of the TPR Domain of p67phox in Complex with Rac·GTP
Lapouge, K., Smith, S. J. M., Walker, P. A., Gamblin, S. J., Smerdon, S. J., & Rittinger, K. (2000) · Molecular Cell · doi:10.1016/s1097-2765(05)00091-2 · Cited by 311 · see citing works
Rho GTPase signaling in cancer progression and dissemination
Crosas‐Molist, E., Samain, R., Kohlhammer, L., Orgaz, J. L., George, S. L., Maiques, Ó., Barcelo, J., & Sanz‐Moreno, V. (2021) · Physiological Reviews · doi:10.1152/physrev.00045.2020 · Cited by 277 · see citing works
Involvement of Rac1 in Activation of Multicomponent Nox1- and Nox3-Based NADPH Oxidases
Ueyama, T., Geiszt, M., & Leto, T. L. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.26.6.2160-2174.2006 · Cited by 230 · see citing works
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Glucosylation and ADP Ribosylation of Rho Proteins: Effects on Nucleotide Binding, GTPase Activity, and Effector Coupling
Sehr, P. A., Joseph, G., Genth, H., Just, I., Pick, E., & Aktories, K. (1998) · Biochemistry · doi:10.1021/bi972592c · Cited by 215 · see citing works
A Rac1 Effector Site Controlling Mitogenesis through Superoxide Production
Joneson, T., & Bar‐Sagi, D. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.29.17991 · Cited by 185 · see citing works
Discussion
Irani, K., & Pj, G.-C. (1998) · Biochemical Pharmacology · doi:10.1016/s0006-2952(97)00616-3 · Cited by 159 · see citing works
Activation of the small GTPase Rac is sufficient to disrupt cadherin-dependent cell-cell adhesion in normal human keratinocytes.
Braga, V. M. M., Betson, M., Li, X.-D., & Lamarche-Vane, N. (2000) · Molecular Biology of the Cell · doi:10.1091/mbc.11.11.3703 · Cited by 173 · see citing works
NADPH Oxidase Activity Is Independent of p47
Freeman, J. L. R., & Lambeth, J. D. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.37.22578 · Cited by 157 · see citing works
Rac “Insert Region” Is a Novel Effector Region That Is Implicated in the Activation of NADPH Oxidase, but Not PAK65
Freeman, J. L. R., Abo, A., & Lambeth, J. D. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.33.19794 · Cited by 155 · see citing works
Rac Binding to p67
Nisimoto, Y., Freeman, J. L. R., Motalebi, S. A., Hirshberg, M., & Lambeth, J. D. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.30.18834 · Cited by 138 · see citing works
Dual Role of Rac in the Assembly of NADPH Oxidase, Tethering to the Membrane and Activation of p67
Sarfstein, R., Gorzalczany, Y., Mizrahi, A., Berdichevsky, Y., Molshanski-Mor, S., Weinbaum, C., Hirshberg, M., Dagher, M., & Pick, E. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m312394200 · Cited by 138 · see citing works
Direct Involvement of the Small GTPase Rac in Activation of the Superoxide-producing NADPH Oxidase Nox1
Miyano, K., Ueno, N., Takeya, R., & Sumimoto, H. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m513665200 · Cited by 137 · see citing works
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Phosphatidic Acid and Diacylglycerol Directly Activate NADPH Oxidase by Interacting with Enzyme Components
Palicz, A., Foubert, T. R., Jesaitis, A. J., Maródi, L., & McPhail, L. C. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m007759200 · Cited by 116 · see citing works
Trp56 of Rac1 Specifies Interaction with a Subset of Guanine Nucleotide Exchange Factors
Gao, Y., Xing, J., Streuli, M., Leto, T. L., & Zheng, Y. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m108865200 · Cited by 115 · see citing works
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Human Monocytes Use Rac1, Not Rac2, in the NADPH Oxidase Complex
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Divergence of Mechanisms Regulating Respiratory Burst in Blood and Sputum Eosinophils and Neutrophils from Atopic Subjects
Lacy, P., Latif, D. A., Steward, M., Musat‐Marcu, S., Man, S. F. P., & Moqbel, R. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.170.5.2670 · Cited by 100 · see citing works
Role of the Rho GTPase Rac in the activation of the phagocyte NADPH oxidase
Pick, E. (2014) · Small GTPases · doi:10.4161/sgtp.27952 · Cited by 98 · see citing works
Antagonistic Cross-talk between Rac and Cdc42 GTPases Regulates Generation of Reactive Oxygen Species
Diebold, B. A., Fowler, B. J., Lu, J., Dinauer, M. C., & Bokoch, G. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m313891200 · Cited by 94 · see citing works
GTPases and reactive oxygen species: switches for killing and signaling
Werner, E. (2003) · Journal of Cell Science · doi:10.1242/jcs.00937 · Cited by 92 · see citing works
Rac regulates PtdInsP3 signaling and the chemotactic compass through a redox-mediated feedback loop
Kuiper, J. W., Sun, C., Magalhães, M. A. O., & Glogauer, M. (2011) · Blood · doi:10.1182/blood-2010-09-310383 · Cited by 70 · see citing works
Assembly of the phagocyte NADPH oxidase complex: chimeric constructs derived from the cytosolic components as tools for exploring structure-function relationships
Mizrahi, A., Berdichevsky, Y., Ugolev, Y., Molshanski-Mor, S., Nakash, Y., Dahan, I. M., Alloul, N., Gorzalczany, Y., Sarfstein, R., Hirshberg, M., et al. (2006) · Journal of Leukocyte Biology · doi:10.1189/jlb.1005553 · Cited by 66 · see citing works
" Peptide Walking" Is a Novel Method for Mapping Functional Domains in Proteins
Joseph, G., & Pick, E. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.49.29079 · Cited by 65 · see citing works
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Alloul, N., Gorzalczany, Y., Itan, M., Sigal, N., & Pick, E. (2001) · Biochemistry · doi:10.1021/bi0117347 · Cited by 65 · see citing works
Rac2 Regulates Neutrophil Chemotaxis, Superoxide Production, and Myeloid Colony Formation through Multiple Distinct Effector Pathways
Carstanjen, D., 山内, 明., Koornneef, A., Zang, H., Filippi, M., Harris, C. E., Towe, J., Atkinson, S. J., Zheng, Y., Dinauer, M. C., et al. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.174.8.4613 · Cited by 61 · see citing works
Mutational Analysis of Novel Effector Domains in Rac1 Involved in the Activation of Nicotinamide Adenine Dinucleotide Phosphate (Reduced) Oxidase
Toporik, A., Gorzalczany, Y., Hirshberg, M., Pick, E., & Lotan, O. (1998) · Biochemistry · doi:10.1021/bi9800404 · Cited by 60 · see citing works
The Renaturable 69- and 63-kDa Protein Kinases That Undergo Rapid Activation in Chemoattractant-stimulated Guinea Pig Neutrophils Are p21-Activated Kinases
Ding, J., Knaus, U. G., Lian, J. P., Bokoch, G., & Badwey, J. A. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.40.24869 · Cited by 52 · see citing works
Expression of nonphagocytic NADPH oxidase system in the ocular lens.
Rao, P. V., Maddala, R., John, F., & Zigler, J. S. (2004) · PubMed · Cited by 50 · see citing works
Specificity of Rho Insert-mediated Activation of Phospholipase D1
Walker, S. J., & Brown, H. A. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m201811200 · Cited by 46 · see citing works
The role of Rho GTPases and SNAREs in mediator release from granulocytes
Lacy, P. (2005) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2005.03.008 · Cited by 45 · see citing works
Rac1 Disrupts p67phox/p40phox Binding: A Novel Role for Rac in NADPH Oxidase Activation
Rinckel, L. A., Faris‐Young, S. L., Hitt, N. D., & Kleinberg, M. E. (1999) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1999.1334 · Cited by 44 · see citing works
The role of phosphoinositides and phosphorylation in regulation of NADPH oxidase
Perišić, O., Wilson, M. I., Karathanassis, D., Bravo, J., Pacold, M. E., Ellson, C. D., Hawkins, P. T., Stephens, L., & Williams, R. L. (2004) · Advances in Enzyme Regulation · doi:10.1016/j.advenzreg.2003.11.003 · Cited by 43 · see citing works
The Insert Region of Rac1 Is Essential for Membrane Ruffling but Not Cellular Transformation
Karnoub, A. E., Der, C. J., & Campbell, S. L. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.8.2847-2857.2001 · Cited by 42 · see citing works
The insert region of the Rac GTPases is dispensable for activation of superoxide-producing NADPH oxidases
Miyano, K., Koga, H., Minakami, R., & Sumimoto, H. (2009) · Biochemical Journal · doi:10.1042/bj20082182 · Cited by 39 · see citing works
Regulation of the Phagocyte Respiratory Burst Oxidase by Protein Interactions
Lambeth, J. D. (2000) · BMB Reports · Cited by 38 · see citing works
Stress, superoxide, and signal transduction.
Goldschmidt‐Clermont, P. J., & Moldovan, L. (1999) · Europe PMC (PubMed Central) · Cited by 37 · see citing works
Specific Recognition of Rac2 and Cdc42 by DOCK2 and DOCK9 Guanine Nucleotide Exchange Factors
Kwofie, M. A., & Skowronski, J. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m705170200 · Cited by 36 · see citing works
Rho GTPases and the Control of the Oxidative Burst in Polymorphonuclear Leukocytes
Diebold, B. A., & Bokoch, G. (2005) · Current topics in microbiology and immunology · doi:10.1007/3-540-27511-8_6 · Cited by 36 · see citing works
Assessment of the Role for Rho Family GTPases in NADPH Oxidase Activation
Miyano, K., & Sumimoto, H. (2011) · Methods in molecular biology · doi:10.1007/978-1-61779-442-1_14 · Cited by 34 · see citing works
Cell-Free NADPH Oxidase Activation Assays: “In Vitro Veritas”
Pick, E. (2014) · Methods in molecular biology · doi:10.1007/978-1-62703-845-4_22 · Cited by 31 · see citing works
Clinical and functional spectrum of RAC2-related immunodeficiency
Donkó, Á., Sharapova, S. O., Kabát, J., Ganesan, S., Hauck, F. H., Bergerson, J., Marois, L., Abbott, J. K., Moshous, D., Williams, K. W., et al. (2024) · Blood · doi:10.1182/blood.2023022098 · Cited by 30 · see citing works
Self-citation
Rac-dependent feedforward autoactivation of NOX2 leads to oxidative burst
Hoang, H. M., Johnson, H. E., & Heo, J. (2021) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2021.100982 · Cited by 29 · see citing works
Evolutionary and structural analyses of the NADPH oxidase family in eukaryotes reveal an initial calcium dependency
Massari, M., Nicoll, C. R., Marchese, S., Mattevi, A., & Mascotti, M. L. (2022) · Redox Biology · doi:10.1016/j.redox.2022.102436 · Cited by 28 · see citing works
Agonist Activation of F-Actin-Mediated Eosinophil Shape Change and Mediator Release Is Dependent on Rac2
Lacy, P., Willetts, L., Kim, J. D., Lo, A. N., Lam, B. D., MacLean, E., Moqbel, R., Rothenberg, M. E., & Zimmermann, N. (2011) · International Archives of Allergy and Immunology · doi:10.1159/000322597 · Cited by 28 · see citing works
Soluble Regulatory Proteins for Activation of NOX Family NADPH Oxidases
Sumimoto, H., Minakami, R., & Miyano, K. (2019) · Methods in molecular biology · doi:10.1007/978-1-4939-9424-3_8 · Cited by 23 · see citing works
Impact of amino acids 22–27 of Rho‐subfamily GTPases on glucosylation by the large clostridial cytotoxins TcsL‐1522, TcdB‐1470 and TcdB‐8864
Müller, S., von Eichel‐Streiber, C., & Moos, M. (1999) · European Journal of Biochemistry · doi:10.1046/j.1432-1327.1999.00951.x · Cited by 19 · see citing works
Inhibitory effects of a dominant-interfering form of the Rho-GTPase Cdc42 in the chemoattractant-elicited signaling pathways leading to NADPH oxidase activation in differentiated HL-60 cells
Rabiet, M., Tardif, M., Braun, L., & Boulay, F. (2002) · Blood · doi:10.1182/blood-2001-12-0193 · Cited by 19 · see citing works
NADPH Oxidase 3: Beyond the Inner Ear
Herb, M. (2024) · Antioxidants · doi:10.3390/antiox13020219 · Cited by 18 · see citing works
Focus on FOCIS: The continuing diagnostic challenge of autosomal recessive chronic granulomatous disease
Yu, G. P., Hong, D. K., Dionis, K. Y., Rae, J., Heyworth, P. G., Curnutte, J. T., & Lewis, D. B. (2008) · Clinical Immunology · doi:10.1016/j.clim.2008.05.008 · Cited by 18 · see citing works
Phagocyte NADPH Oxidase p67-phoxPossesses a Novel Carboxylterminal Binding Site for the GTPases Rac2 and Cdc42
Faris‐Young, S. L., Rinckel, L. A., Huang, J., Hong, Y., & Kleinberg, M. E. (1998) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1998.8775 · Cited by 17 · see citing works
Cdc42 regulates reactive oxygen species production in the pathogenic yeast Candida albicans
Kowalewski, G. P., Wildeman, A. S., Bogliolo, S., Besold, A. N., Bassilana, M., & Culotta, V. (2021) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2021.100917 · Cited by 13 · see citing works
Protocadherin-7 Regulates Osteoclast Differentiation through Intracellular SET-Binding Domain-Mediated RhoA and Rac1 Activation
Kim, H., Takegahara, N., & Choi, Y. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222313117 · Cited by 13 · see citing works
p67phox binds to a newly identified site in Nox2 following the disengagement of an intramolecular bond—Canaan sighted?
Bechor, E., Zahavi, A., Amichay, M., Fradin, T., Federman, A., Berdichevsky, Y., & Pick, E. (2020) · Journal of Leukocyte Biology · doi:10.1002/jlb.4a1219-607r · Cited by 11 · see citing works
Components and Organisation of the NADPH Oxidase of Phagocytic Cells, the Paradigm for an Electron Transport Chain across the Plasma Membrane
Segal, A. W., Wientjes, F. B., Stockley, R. W., & Dekker, L. V. (1998) · Springer eBooks · doi:10.1007/978-94-017-2695-5_3 · Cited by 11 · see citing works
The role of Rho GTPases’ substrates Rac and Cdc42 in osteoclastogenesis and relevant natural medicinal products study
Liu, Y., Dou, Y.-S., Yan, L. W., Yang, X., He, B., Kong, L., & Smith, W. W. (2020) · Bioscience Reports · doi:10.1042/bsr20200407 · Cited by 10 · see citing works
The Regulatory Role of Rho GTPases and their Substrates in Osteoclastogenesis
Gao, L., Kong, L., & Zhao, Y.-T. (2020) · Current Drug Targets · doi:10.2174/1389450121666200925150446 · Cited by 10 · see citing works
Components and organization of the nadph oxidase of phagocytic cells
Segal, A. W., Wientjes, F. B., Stockley, R. W., & Dekker, L. V. (1999) · Advances in cellular and molecular biology of membranes and organelles · doi:10.1016/s1874-5172(99)80043-1 · Cited by 9 · see citing works
Structure and Regulation of NADPH Oxidase of Phagocytic Leukocytes
Heyworth, P. G., Curnutte, J. T., & Badwey, J. A. (1999) · Humana Press eBooks · doi:10.1007/978-1-59259-253-1_8 · Cited by 9 · see citing works
The molecular basis of Rac-GTP action—promoting binding of p67phoxto Nox2 by disengaging the β hairpin from downstream residues
Bechor, E., Zahavi, A., Berdichevsky, Y., & Pick, E. (2021) · Journal of Leukocyte Biology · doi:10.1002/jlb.4hi1220-855rr · Cited by 8 · see citing works
Paradigm Shifts in the History of Nox2 and Its Regulators: An Appreciative Critique
Pick, E. (2023) · Springer eBooks · doi:10.1007/978-3-031-23752-2_1 · Cited by 3 · see citing works
Rac, Superoxide, and Signal Transduction
Hassanain, H. H., & Goldschmidt‐Clermont, P. J. (2000) · Elsevier eBooks · doi:10.1016/b978-012636670-9/50005-2 · Cited by 3 · see citing works
)ELIJSKA SIGNALNA TRANSDUKCIJA - MODULACIJA SLOBODNIM RADIKALIMA
Koci, G. (2002) · Cited by 3 · see citing works
The three-dimensional model of Dictyostelium discoideum racE based on the human rhoA-GDP crystal structure
Agarwal, M., Nelson, D. J., & Larochelle, D. A. (2002) · Journal of Molecular Graphics and Modelling · doi:10.1016/s1093-3263(01)00137-1 · Cited by 2 · see citing works
Regulation of the NADPH Oxidase by Rac GTPase
Diebold, B. A., & Bokoch, G. (2003) · Elsevier eBooks · doi:10.1016/b978-012124546-7/50599-4 · Cited by 1 · see citing works
Regulation of NADPH Oxidases by Rac GTPase
Bokoch, G., Gianni, D., Kim, J., & Kao, Y.-Y. (2010) · Elsevier eBooks · doi:10.1016/b978-0-12-374145-5.00216-3
The NADPH Oxidase Activator p67phox and Its Related Proteins
Sumimoto, H., Kohda, A., Hayase, J., & Kamakura, S. (2023) · Springer eBooks · doi:10.1007/978-3-031-23752-2_16
RAC2-Related Immunodeficiency
Hsu, A. P. (2026) · Springer eBooks · doi:10.1007/978-3-032-21135-4_20
Falling in Love with Nox2: My Journey to Ithaka (A Scientific Autobiography)
Pick, E. (2026) · Springer eBooks · doi:10.1007/978-3-032-21135-4_1

Mutational Analysis of Novel Effector Domains in Rac1 Involved in the Activation of Nicotinamide Adenine Dinucleotide Phosphate (Reduced) Oxidase
Toporik, A., Gorzalczany, Y., Hirshberg, M., Pick, E., & Lotan, O. (1998) · Biochemistry · doi:10.1021/bi9800404 · Cited by 60 · see citing works
Dual Role of Rac in the Assembly of NADPH Oxidase, Tethering to the Membrane and Activation of p67phox A STUDY BASED ON MUTAGENESIS OF p67phox-Rac1 CHIMERAS*
Pick, E. (2015)
Dual Role of Rac in the Assembly of NADPH Oxidase, Tethering to the Membrane and Activation of p67
Sarfstein, R., Gorzalczany, Y., Mizrahi, A., Berdichevsky, Y., Molshanski-Mor, S., Weinbaum, C., Hirshberg, M., Dagher, M., & Pick, E. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m312394200 · Cited by 138 · see citing works
The Rac Target NADPH Oxidase p67 Interacts Preferentially with Rac2 Rather Than Rac1
Dorseuil, O., Reibel, L., Bokoch, G., Camonis, J., & Gâcon, G. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.1.83 · Cited by 108 · see citing works
Interaction of Rac with p67 phox and Regulation pf Phagocytic NADPH Oxidase Activity
Diekmann, D., Abo, A., Johnston, C. L., Segal, A. W., & Hall, A. (1994) · Science · doi:10.1126/science.8036496 · Cited by 382 · see citing works

Authors: Kwong, C. H., Adams, A. G., & Leto, T. L.
Affiliations: National Institutes of Health (US)
ORCID: Leto, Thomas L.
Venue: Journal of Biological Chemistry
Publisher: Elsevier BV
Published: 1995-08
Volume: 270
Issue: 34
Pages: 19868-19872
ISSN: 0021-9258 (ISSN-L)
DOI: 10.1074/jbc.270.34.19868
OpenAlex: W2038894510
Cited by: 76
References: 42
Citations by year: 2026: 2 · 2025: 1 · 2024: 2 · 2023: 2 · 2022: 1 · 2021: 5 · 2020: 3 · 2019: 1 · 2014: 2
FWCI: 1.49
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by/4.0/ (vor, 9215 d)
Locations: Journal of Biological Chemistry (publishedVersion, cc-by)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
Keywords: Rac, NADPH oxidase activation, Cdc42, Rac1, Rac2, p47phox, p67phox, flavocytochrome b558, fusion protein, point mutagenesis, phagocytic leukocytes, G proteins
MeSH terms: Amino Acid Sequence, Animals, Binding Sites, Enzyme Activation, Humans, Molecular Sequence Data, Mutation, NADH, NADPH Oxidoreductases, Neutrophils, Oxidation-Reduction, Recombinant Fusion Proteins, Structure-Activity Relationship, Sequence Homology, Amino Acid, Cell Cycle Proteins, GTP-Binding Proteins, NADPH Oxidases, rac GTP-Binding Proteins, cdc42 GTP-Binding Protein, In Vitro Techniques

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Characterization of the Effector-specifying Domain of Rac Involved in NADPH Oxidase Activation

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