Regulation of the phagocyte NADPH oxidase by Rac GTPase

Antioxidants and Redox Signaling

Volumn 8, Issue 9-10, 2006, Pages 1533-1548

  Bokoch, Gary M ^a,b   Zhao, Tieming ^a  

^a SCRIPPS RESEARCH INSTITUTE   (United States)

^b IMM14 ^*  (United States)

Author keywords

[No Author keywords available]

Indexed keywords

GUANOSINE TRIPHOSPHATASE; OXIDOREDUCTASE; PHAGOCYTE OXIDOREDUCTASE; RAC PROTEIN; REACTIVE OXYGEN METABOLITE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE OXIDASE; UNCLASSIFIED DRUG;

COMPLEX FORMATION; CYTOSOL; ENZYME ACTIVATION; ENZYME ACTIVE SITE; ENZYME ACTIVITY; ENZYME REGULATION; HUMAN; INNATE IMMUNITY; LEUKOCYTE; NONHUMAN; PHAGOCYTOSIS; PRIORITY JOURNAL; PROTEIN ASSEMBLY; PROTEIN PROTEIN INTERACTION; REGULATORY MECHANISM; REVIEW;

ANIMALS; CDC42 GTP-BINDING PROTEIN; CYTOCHROMES B; HUMANS; MODELS, BIOLOGICAL; NADPH OXIDASE; NEUTROPHILS; PHAGOCYTES; RAC GTP-BINDING PROTEINS; REACTIVE OXYGEN SPECIES;

MAMMALIA;

EID: 33750924781     PISSN: 15230864     EISSN: None     Source Type: Journal    
DOI: 10.1089/ars.2006.8.1533     Document Type: Review

References (128)

1. Morel F, Doussiere J, and Vignais PY The superoxide-generating oxidase of phagocytic cells: physiological, molecular and pathological aspects. Eur J Biochem 201: 523-546, 1991.
2. Cross AR and Segal AW. The NADPH oxidase of professional phagocytes-prototype of the NOX electron transport chain systems. Biochim Biophys Acta 1657: 1-22, 2004.
3. Lambeth JD. NOX enzymes and the biology of reactive oxygen. Nat Rev Immunol 4: 181-189, 2004.
4. Bokoch GM and Knaus UG. NADPH oxidases: Not just for leukocytes anymore! Trends Biochem Sci 28: 502-508, 2003.
5. Smith RM and Curnutte JT. Molecular basis of chronic granulomatous disease. Blood 77: 673-686, 1991.
6. Lapouge K, Smith SJ, Groemping Y, and Rittinger K. Architecture of the p40-p47-p67phox complex in the resting state of the NADPH oxidase: A central role for p67phox. J Biol Chem 277: 10121-10128, 2002.
7. Wientjes FB, Panayotou G, Reeves E, and Segal AW. Interactions between cytosolic components of the NADPH oxidase: p40phox interacts with both p67phox and p47phox. Biochem J 317: 919-924, 1996.
8. DeLeo FR and Quinn MT. Assembly of the phagocyte NADPH oxidase: molecular interaction of oxidase proteins. J Leukoc Biol 60: 677-691, 1996.
9. Lambeth JD. Regulation of the phagocyte respiratory burst oxidase by protein interactions. Biochem Mol Biol Int 33: 427-439, 2000.
10. Groemping Y and Rittinger K. Activation and assembly of the NADPH oxidase: a structural perspective. Biochem J 386: 401-416, 2005.
11. Sheppard FR, Kelher MR, Moore EE, McLaughlin NJ, Banerjee A, and Silliman CC. Structural organization of the neutrophil NADPH oxidase: phosphorylation and translocation during priming and activation. J Leukoc Biol 78: 1025-1042, 2005.
12. Babior BM. NADPH oxidase. Curr Opin Immunol 16: 42-47, 2004.
13. Kanai F, Liu H, Field SJ, Akbary H, Matsuo T, Brown GE, Cantley LC, and Yaffe MB. The PX domains of p47phox and p40phox bind to lipid products of PI(3)K. Nat Cell Biol 3: 675-678, 2001.
14. Zhan Y, Virbasius JV, Song X, Pomerleau DP, and Zhou GW. The p40phox and p47phox PX domains of NADPH oxidase target cell membranes via direct and indirect recruitment by phosphoinositides. J Biol Chem 277: 4512-4518, 2002.
15. Ago T, Kuribayashi F, Hiroaki H, Takeya R, Ito T, Kohda D, and Sumimoto H. Phosphorylation of p47phox directs phox homology domain from SH3 domain toward phosphoinositides, leading to phagocyte NADPH oxidase activation. Proc Natl Acad Sci U S A 100: 4474-4479, 2003.
16. Freeman JL and Lambeth JD. NADPH oxidase activity is independent of p47phox in vitro. J Biol Chem 271: 22578-22582, 1996.
17. Koshkin V, Lotan O, and Pick E. The cytosolic component p47(phox) is not a sine qua non participant in the activation of NADPH oxidase but is required for optimal superoxide production. J Biol Chem 271: 30326-30329, 1996.
18. Matute JD, Arias AA, Dinauer MC, and Patino PJ. p40phox: the last NADPH oxidase subunit. Blood Cells Mol Dis 35: 291-302, 2005.
19. Wientjes FB, Hsuan JJ, Totty NF, and Segal AW. p40phox, a third cytosolic component of the activation complex of the NADPH oxidase to contain src homology 3 domains. Biochem J 296: 557-561, 1993.
20. Suh C, Stull N, Fujii Y, Grinstein S, and Yaffe M et al. 2006. Blood 104: 188a (Abstr.)
21. Ellson CD, Gobert-Gosse S, Anderson KE, Davidson K, Erdjument-Bromage H, Tempst P, Thuring JW, Cooper MA, Lim ZY, Holmes AB, Gaffney PR, Coadwell J, Chilvers ER, Hawkins PT, and Stephens LR. PtdIns(3)P regulates the neutrophil oxidase complex by binding to the PX domain of p40(phox). Nat Cell Biol 3: 679-682, 2001.
22. Vieira OV, Botelho RJ, Rameh L, Brachmann SM, Matsuo T, Davidson HW, Schreiber A, Backer JM, Cantley LC, and Grinstein S. Distinct roles of class 1 and class III phosphatidylinositol 3-kinases in phagosome formation and maturation. J Cell Biol 155: 19-25, 2001.
23. He R, Nanamori M, Sang H, Yin H, Dinauer MC, and Ye RD. Reconstitution of chemotactic peptide-induced nicotinamide adenine dinucleotide phosphate (reduced) oxidase activation in transgenic COS-phox cells. J Immunol 173: 7462-7470, 2004.
24. Kuribayashi F, Nunoi H, Wakamatsu K, Tsunawaki S, Sato K, Ito T, and Sumimoto H. The adaptor protein p40(phox) as a positive regulator of the superoxide-producing phagocyte oxidase. EMBO J 21: 6312-6320, 2002.
25. Han CH, Freeman JL, Lee T, Motalebi SA, and Lambeth JD. Regulation of the neutrophil respiratory burst oxidase: identification of an activation domain in p67(phox). J Biol Chem 273: 16663-16668, 1998.
26. Grizot S, Fieschi F, Dagher MC, and Pebay-Peyroula E. The active N-terminal region of p67phox: structure at 1.8 A resolution and biochemical characterizations of the A128V mutant implicated in chronic granulomatous disease. J Biol Chem 276: 21627-21631, 2001.
27. Nishimoto Y, Notalebi S, and Lambeth JD. The p67 phox activation domain regulates electron transfer flow from NADPH to flavin in flavocytochrome b558. J Biol Chem 274: 22999-23005, 1999.
28. Koga H, Terasawa H, Nunoi H, Takeshige K, Inagaki F, and Sumimoto H. Tetratricopeptide repeat (TPR) motifs of p67(phox) participate in interaction with the small GTPase Rac and activation of the phagocyte NADPH oxidase. J Biol Chem 274: 25051-25060, 1999.
29. phox in complex with Rac-GTP. Mol Cell 6: 899-907, 2000.
30. Diebold BA and Bokoch GM. Molecular basis for Rac2 regulation of phagocyte NADPH oxidase. Nat Immunol 2: 211-215, 2001.
31. Gorzalczany Y, Alloul N, Sigal N, Weinbaum C, and Pick E. A prenylated p67phox-Rac1 chimera elicits NADPH-dependent superoxide production by phagocyte membranes in the absence of an activator and of p47phox: conversion of a pagan NADPH oxidase to monotheism. J Biol Chem 277: 18605-18610, 2002.
32. Sarfstein R, Gorzalczany Y, Mizrahi A, Berdichevsky Y, Molshanski-Mor S, Weinbaum C, Hirshberg M, Dagher MC, and Pick E. 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. J Biol Chem 279: 16007-16016, 2004.
33. van Bruggen R, Anthony E, Fernandez-Borja M, and Roos D. Continuous translocation of Rac2 and the NADPH oxidase component p67(phox) during phagocytosis. J Biol Chem 279: 9097-9102, 2004.
34. Bokoch GM and Diebold BA. Current molecular models for NADPH oxidase regulation by Rac GTPase. Blood 100: 2692-2696, 2002.
35. Dinauer MC. Regulation of neutrophil function by Rac GTPases. Curr Opin Hematol 10: 8-15, 2003.
36. Knaus UG, Heyworth PG, Evans T, Curnutte JT, and Bokoch GM. Regulation of phagocyte oxygen radical production by the GTP-binding protein Rac 2. Science 254: 1512-1515, 1991.
37. Abo A, Pick E, Hall A, Totty N, Teahan CG, and Segal AW Activation of the NADPH oxidase involves the small GTP-binding protein p21rac1. Nature 353: 668-670, 1991.
38. Quinn MT, Evans T, Loetterle LR, Jesaitis AJ, and Bokoch GM. Translocation of Rac correlates with NADPH oxidase activation: evidence for equimolar translocation of oxidase components. J. Biol Chem 268: 20983-20987, 1993.
39. Voncken JW, van SH, Kaartinen V, Deemer K, Coates T, Landing B, Pattengale P, Dorseuil O, Bokoch GM, and Groffen J. Increased neutrophil respiratory burst in bcr-null mutants. Cell 80: 719-728, 1995.
40. Dorseuil O, Vazquez A, Lang P, Bertoglio J, Gacon G, and Leca G. Inhibition of superoxide production in B lymphocytes by rac antisense oligonucleotides. J Biol Chem 267: 20540-20542, 1992.
41. Roberts AW, Kim C, Zhen L, Lowe JB, Kapur R, Petrynlak B, Spaetti A, Pollock J, Borneo JB, Bradford GB, Atkinson SJ, Dinauer MC, and Williams DA. Deficiency of the hematopoietic cell-specific Rho family GTPase Rac2 is characterized by abnormalities in neutrophil function and host defense. Immunity 10: 1-20, 1999.
42. Kim C and Dinauer MC. Rac2 is an essential regulator of neutrophil nicotinamide adenine dinucleotide phosphate oxidase activation in response to specific signaling pathways. J Immunol 166: 1223-1232, 2001.
43. Li S, Yamauchi A, Marchal CC, Molitoris JK, Quilliam LA, and Dinauer MC. Chemoattractant-stimulated Rac activation in wild-type and Rac2-deficient murine neutrophils: preferential activation of Rac2 and Rac2 gene dosage effect on neutrophil functions. J Immunol 169: 5043-5051, 2002.
44. Glogauer M, Marchal CC, Zhu F, Worku A, Clausen BE, Foerster I, Marks P, Downey GP, Dinauer MC, and Kwiatkowski DJ. Rac1 deletion in mouse neutrophils has selective effects on neutrophil functions. J Immunol 170: 5652-5657, 2003.
45. Yamauchi A, Kim C, Li S, Marchal CC, Towe J, Atkinson SJ, and Dinauer MC. Rac2-deficient murine macrophages have selective defects in superoxide production and phagocytosis of opsonized particles. J Immunol 173: 5979-6004.
46. Zhao X, Carnevale KA, and Cathcart MK. Human monocytes use Rac1, not Rac2, in the NADPH oxidase complex. J Biol Chem 278: 40788-40792, 2003.
47. Williams DA, Tao W, Yang F, Kim C, Gu Y, Mansfield P, Levine JE, Petryniak B, Derrow CW, Harris C, Jia B, Zheng Y, Ambruso DR, Lowe JB, Atkinson SJ, Dinauer MC, and Boxer L. Dominant negative mutation of the hematopoietic-specific GTPase, Rac2, is associated with a human phagocyte immunodeficiency. Blood 96: 1646-1654, 2000.
48. Ambruso DR, Knall C, Abell AN, Panepinto J, Kurkchubasche A, Thurman G, Gonzalez-Aller C, Hiester A, deBoer M, Harbeck RJ, Oyer R, Johnson GL, and Roos D. Human neutrophil immunodeficiency syndrome is associated with an inhibitory Rac2 mutation. Proc Natl Acad Sci U S A 97: 4654-4659, 2000.
49. Van Aelst L and Souza-Schorey C. Rho GTPases and signaling networks. Genes Dev 11: 2295-2322, 1997.
50. Jaffe AB and Hall A. RHO GTPASES: Biochemistry and biology. Annu Rev Cell Dev Biol 21: 247-269, 2005.
51. Vetter IR and Wittinghofer A. The guanine nucleotide-binding switch in three dimensions. Science 294: 1299-1304, 2001.
52. DerMardirossian C and Bokoch GM. GDIs: Central regulatory molecules in Rho GTPase activation. Trends Cell Biol 15: 356-363, 2005.
53. Zhou K, Wang Y, Gorski JL, Nomura N, Collard J, and Bokoch GM. Guanine nucleotide exchange factors regulate specificity of downstream signaling from Rac and Cdc42. J Biol Chem 273: 16782-16786, 1998.
54. Connolly BA, Rice J, Feig LA, and Buchsbaum RJ. Tiam1-IRSp53 complex formation directs specificity of rac-mediated actin cytoskeleton regulation. Mol Cell Biol 25: 4602-4614, 2005.
55. Fu HW and Casey PJ. Enzymology and biology of CaaX protein prenylation. Recent Prog Horm Res 54: 315-342, 1999.
56. Kloog Y and Cox AD. Prenyl-binding domains: potential targets for Ras inhibitors and anti-cancer drugs. Semin Cancer Biol 14: 253-261, 2004.
57. Molnar G, Dagher MC, Geiszt M, Settleman J, and Ligeti E. Role of prenylation in the interaction of Rho-family small GTPases with GTPase activating proteins. Biochemistry 40: 10542-10549, 2001.
58. Heyworth PG, Knaus UG, Xu X, Uhlinger DJ, Conroy L, Bokoch GM, and Curnutte JT. Requirement for posttranslational processing of Rac GTP-binding proteins for activation of human neutrophil NADPH oxidase. Mol Biol Cell 4: 261-269, 1993.
59. Chuang TH, Bohl BP, and Bokoch GM. Biologically-active lipids are regulators of Rac-GDI complexation. J Biol Chem 268: 26206-26211, 1993.
60. DerMardirossian C, Schnelzer A, and Bokoch GM. Phosphorylation of RhoGDI by Pak1 mediates dissociation of Rac GTPase. Mol Cell 15: 117-127, 2004.
61. Faure J, Vignais PV, and Dagher MC. Phosphoinositide-dependent activation of A involves partial opening of the RhoA/Rho-GDI complex. Eur J Biochem 262: 879-889, 1999.
62. Mizuno T, Kaibuchi K, Ando S, Musha T, Hiraoka K, Takaishi K, Asada M, Nunoi H, Matsuda I, and Takai Y. Regulation of the superoxide-generating NADPH oxidase by a small GTP-binding protein and its stimulatory and inhibitory GDP/GTP exchange proteins. J Biol Chem 267: 10215-10218, 1992.
63. Mizrahi A, Molshanski-Mor S, Weinbaum C, Zheng Y, Hirshberg M, and Pick E. Activation of the phagocyte NADPH oxidase by Rac guanine nucleotide exchange factors in conjunction with ATP and nucleoside diphosphate kinase. J Biol Chem 280: 3802-3811, 2005.
64. Hirshberg M, Stockley RW, Dodson G, and Webb MR. The crystal structure of human rac1, a member of the rho-family complexed with a GTP analogue. Nat Struct Biol 4: 147-152, 1997.
65. Freeman JL, Kreck ML, Uhlinger DJ, and Lambeth JD. Ras effector-homologue region on Rac regulates protein associations in the neutrophil respiratory burst oxidase complex. Biochemistry 33: 13431-13435, 1994.
66. Xu X, Barry DC, Settleman J, Schwartz MA, and Bokoch GM. Differing structural requirements for GTPase-activating protein responsiveness and NADPH oxidase activation by Rac. J Biol Chem 269: 23569-23574, 1994.
67. Diekmann D, Abo A, Johnston C, Segal AW, and Hall A. Interaction of Rac with p67phox and regulation of phagocytic NADPH oxidase activity. Science 265: 531-533, 1994.
68. Joseph G and Pick E. "Peptide walking" is a novel method for mapping functional domains in proteins: its application to the Rac1-dependent activation of NADPH oxidase. J Biol Chem 270: 29079-29082, 1995.
69. Freeman JL, Abo A, and Lambeth JD. Rac "insert region" is a novel effector region that is implicated in the activation of NADPH oxidase, but not PAK65. J Biol Chem 271: 19794-19801, 1996.
70. Toporik A, Gorzalczany Y, Hirshberg M, Pick E, and Lotan O. Mutational analysis of novel effector domains in Rac1 involved in the activation of nicotinamide adenine dinu-cleotide phosphate (reduced) oxidase. Biochemistry 37: 7147-7156, 1998.
71. Alloul N, Gorzalczany Y, Itan M, Sigal N, and Pick E. Activation of the superoxide-generating NADPH oxidase by chimeric proteins consisting of segments of the cytosolic component p67(phox) and the small GTPase Rac1. Biochemistry 40: 14557-14566, 2001.
72. Heyworth PG, Bohl BP, Bokoch GM, and Curnutte JT. Rac translocates independently of the neutrophil NADPH oxidase components p47-phox and p67-phox: evidence for its interaction with flavocytochrome b558. J Biol Chem 269: 30749-30752, 1994.
73. phox movements in human neutrophils by tyrosine kinase inhibitors. J Leukoc Biol 58: 108-113, 1995.
74. Price MO, Atkinson SJ, Knaus UG, and Dinauer MC. Rac activation induces NADPH oxidase activity in transgenic COSphox cells, and the level of superoxide production is exchange factor-dependent. J Biol Chem 277: 19220-19228, 2002.
75. Knaus UG, Morris S, Dong HJ, Chernoff J, and Bokoch GM. Regulation of human leukocyte p21-activated kinases through G protein-coupled receptors. Science 269: 221-223, 1995.
76. Jones SL, Knaus UG, Bokoch GM, and Brown EJ. Two signaling mechanisms for activation of alphaM beta2 avidity in polymorphonuclear neutrophils. J Biol Chem 273: 10556-10566, 1998.
77. Ago T, Nunoi H, Ito T, and Sumimoto H. Mechanism for phosphorylation- induced activation of the phagocyte NADPH oxidase protein p47(phox): Triple replacement of serines 303, 304, and 328 with aspartates disrupts the SH3 domain-mediated intramolecular interaction in p47(phox), thereby activating the oxidase. J Biol Chem 274: 33644-33653, 1999.
78. Martyn KD, Kim MJ, Quinn MT, Dinauer MC, and Knaus UG. p21-Activated kinase (Pak) regulates NADPH oxidase activation in human neutrophils. Blood 106: 3962-3969, 2005.
79. Shalom-Barak T and Knaus UG. A p21-activated kinase-controlled metabolic switch up-regulates phagocyte NADPH oxidase. J Biol Chem 277: 40659-40665, 2002.
80. Price MO, McPhail LC, Lambeth JD, Han CH, Knaus UG, and Dinauer MC. Creation of a genetic system for analysis of the phagocyte respiratory burst: high-level reconstitution of the NADPH oxidase in a nonhematopoietic system. Blood 99: 2653-2661, 2002.
81. Zhao T, Benard V, Bohl BP, and Bokoch GM. The molecular basis for adhesion-mediated suppression of reactive oxygen species generation by human neutrophils. J Clin Invest 112: 1732-1740, 2003.
82. Gorzalczany Y, Sigal N, Itan M, Lotan O, and Pick E. Targeting of Rac1 to the phagocyte membrane is sufficient for the induction of NADPH oxidase assembly. J Biol Chem 275: 40073-40081, 2000.
83. Rinckel LA, Fans SL, Hitt ND, and Kleinberg ME. Rac1 disrupts p67phox/p40phox binding: a novel role for Rac in NADPH oxidase activation. Biochem Biophys Res Commun 263: 118-122, 1999.
84. Cross AR, Erickson RW, and Curnutte JT. Simultaneous presence of p47(phox) and flavocytochrome b-245 are required for the activation of NADPH oxidase by anionic amphiphiles: evidence for an intermediate state of oxidase activation. J Biol Chem 274: 15519-15525, 1999.
85. Diebold BA, Fowler B, Lu J, Dinauer MC, and Bokoch GM. Antagonistic cross-talk between Rac and Cdc42 GTPases regulates generation of reactive oxygen species. J Biol Chem 279: 28136-28142, 2004.
86. Kwong CH, Malech HL, Rotrosen D, and Leto TL. Regulation of the human neutrophil NADPH oxidase by rho-related G-proteins. Biochemistry 32: 5711-5717, 1993.
87. Benard V, Bohl BP, and Bokoch GM. Characterization of rac and cdc42 activation in chemoattractant-stimulated human neutrophils using a novel assay for active GTPases. J Biol Chem 274: 13198-13204, 1999.
88. Catz SD and Sterin-Speziale NB. Bradykinin stimulates phosphoinositide turnover and phospholipase C but not phospholipase D and NADPH oxidase in human neutrophils. J Leukoc Biol 59: 591-597, 1996.
89. Kozma R, Ahmed S, Best A, and Lim L. The Ras-related protein Cdc42Hs and bradykinin promote formation of peripheral actin microspikes and filopodia in Swiss 3T3 fibroblasts. Mol Cell Biol 15: 1942-1952, 1995.
90. Hoppe AD and Swanson JA. Cdc42, Rac1, and Rac2 display distinct patterns of activation during phagocytosis. Mol Biol Cell 15: 3509-3519, 2004.
91. Hoffstein ST, Gennaro DE, and Manzi RM. Surface contact inhibits neutrophil superoxide generation induced by soluble stimuli. Lab Invest 52: 515-522, 1985.
92. Nathan CF. Neutrophil activation on biological surfaces: Massive secretion of hydrogen peroxide in response to products of macrophages and lymphocytes. J Clin Invest 80: 1550-1560, 1987.
93. Nathan C, Srimal S, Farber C, Sanchez E, Kabbash L, Asch A, Gailit J, and Wright SD. Cytokine-induced respiratory burst of human neutrophils: dependence on extracellular matrix proteins and CD11/CD18 integrins. J Cell Biol 109: 1341-1349, 1989.
94. Liles WC, Ledbetter JA, Waltersdorph AW, and Klebanoff SJ. Cross-linking of CD18 primes human neutrophils for activation of the respiratory burst in response to specific stimuli: implications for adhesion-dependent physiological responses in neutrophils. J Leukoc Biol 58: 690-697, 1995.
95. Shappell SB, Toman C, Anderson DC, Taylor AA, Entman ML, and Smith CW. Mac-1 (CD11b/CD18) mediates adherence-dependent hydrogen peroxide production by human and canine neutrophils. J Immunol 144: 2702-2711, 1990.
96. Dib K, Melander F, Axelsson L, Dagher MC, Aspenstrom P, and Andersson T. Down-regulation of Rac activity during beta 2 integrin-mediated adhesion of human neutrophils. J Biol Chem 278: 24181-24188, 2003.
97. Zhao T and Bokoch GM. Critical role of proline-rich tyrosine kinase 2 in reversion of the adhesion-mediated suppression of reactive oxygen species generation by human neutrophils. J Immunol 174: 8049-8055, 2005.
98. Lokuta MA and Huttenlocher A. TNF-alpha promotes a stop signal that inhibits neutrophil polarization and migration via a p38 MAPK pathway. J Leukoc Biol 78: 210-219, 2005.
99. Thomas PS. Tumour necrosis factor-alpha: the role of this multifunctional cytokine in asthma. Immunol Cell Biol 79: 132-140, 2001.
100. Sivakumar B and Paleolog E. Immunotherapy of rheumatoid arthritis: past, present and future. Curr Opin Drug Discov Dev 8: 169-176, 2005.
101. Sandborn WJ. New concepts in anti-tumor necrosis factor therapy for inflammatory bowel disease. Rev Gastroenterol Disord 5: 10-18, 2005.
102. Dovas A and Couchman JR. RhoGDI: multiple functions in the regulation of Rho family GTPase activities. Biochem J 390: 1-9, 2005.
103. Gardiner EM, Pestonjamasp KN, Bohl B, Chamberlain C, Hahn KM, and Bokoch GM. Spatial and temporal analysis of Rac activation during live neutrophil chemotaxis. Curr Biol 12: 2029-2034, 2002.
104. Decoursey TE and Ligeti E. Regulation and termination of NADPH oxidase activity. Cell Mol Life Sci 62: 2173-2193, 2005.
105. Kim C, Marchal CC, Penninger J, and Dinauer MC. The hemopoietic/Rac guanine nucleotide exchange factor Vavl regulates N-formyl-methionyl-leucyl- phenylalanine-activated neutrophil functions. J Immunol 171: 4425-4430, 2003.
106. Welch HC, Coadwell WJ, Ellson CD, Ferguson GJ, Andrews SR, Erdjument-Bromage H, Tempst P, Hawkins PT, and Stephens LR. P-Rex1, a PtdIns(3,4,5)P3- and Gbetagamma-regulated guanine-nucleotide exchange factor for Rac. Cell 108: 809-821, 2002.
107. Bokoch GM. Chemoattractant signaling and leukocyte activation. Blood 86: 1649-1660, 1995.
108. Dong X, Mo Z, Bokoch G, Guo C, Li Z, and Wu D. P-Rex1 is a primary Rac2 guanine nucleotide exchange factor in mouse neutrophils. Curr Biol 15: 1874-1879, 2005.
109. Welch HC, Condliffe AM, Milne LJ, Ferguson GJ, Hill K, Webb LM, Okkenhaug K, Coadwell WJ, Andrews SR, Thelen M, Jones GE, Hawkins PT, and Stephens LR. P-Rex1 regulates neutrophil function. Curr Biol 15: 1867-1873, 2005.
110. Moskwa P, Dagher MC, Paclet MH, Morel F, and Ligeti E. Participation of Rac GTPase activating proteins in the deactivation of the phagocytic NADPH oxidase. Biochemistry 41: 10710-10716, 2002.
111. Geiszt M, Dagher MC, Molnar G, Havasi A, Faure J, Paclet MH, Morel F, and Ligeti E. Characterization of membrane-localized and cytosolic Rac-GTPase-activating proteins in human neutrophil granulocytes: contribution to the regulation of NADPH oxidase. Biochem J 355: 851-858, 2001.
112. Heyworth PG, Knaus UG, Settleman J, Curnutte JT, and Bokoch GM. Regulation of NADPH oxidase activity by Rac GTPase activating protein(s). Mol Biol Cell 4: 1217-1223, 1993.
113. Dusi S, Donini M, Wientjes F, and Rossi F. Translocation of p190rho guanosine triphosphatase-activating protein from cytosol to the membrane in human neutrophils stimulated with different agonists. Biochem Biophys Res Commun 219: 859-862, 1996.
114. Dorseuil O, Reibel L, Bokoch GM, Camonis J, and Gacon G. The Rac target NADPH oxidase p67phox interacts preferentially with Rac2 rather than Rac1. J Biol Chem. 271: 83-88, 1996.
115. Knaus UG, Wang Y, Reilly AM, Warnock D, and Jackson JH. Structural requirements for PAK activation by Rac GTPases. J Biol Chem 273: 21512-21518, 1998.
116. van Hennik PB, ten Klooster JP, Halstead JR, Voermans C, Anthony EC, Divecha N, and Hordijk PL. The C-terminal domain of Rac1 contains two motifs that control targeting and signaling specificity. J Biol Chem 278: 39166-39175, 2003.
117. Filippi MD, Harris CE, Meller J, Gu Y, Zheng Y, and Williams DA. Localization of Rac2 via the C terminus and aspartic acid 150 specifies superoxide generation, actin polarity and chemotaxis in neutrophils. Nat Immunol 5: 744-751, 2004.
118. Yamauchi A, Marchal CC, Molitoris JK, Pech N, Knaus UG, Towe J, Atkinson SJ, and Dinauer MC. Rac GTPase isoform-specific regulation of NADPH oxidase and chemotaxis in murine neutrophils in vivo: role of the C-terminal polybasic domain. J Biol Chem 10.1074/jbc.M408820200, 2004.
119. Michaelson D, Silletti J, Murphy G, D'Eustachio P, Rush M, and Philips MR. Differential localization of Rho GTPases in live cells: regulation by hypervariable regions and GDI binding. J Cell Biol 152: 111-126, 2001.
120. Haeusler LC, Blumenstein L, Stege P, Dvorsky R, and Ahmadian MR. Comparative functional analysis of the Rac GTPases. FEBS Lett 555: 556-560, 2003.
121. Sumimoto H, Miyano K, and Takeya R. Molecular composition and regulation of the Nox family NAD(P)H oxidases. Biochem Biophys Res Commun 338: 677-686, 2005.
122. Quinn MT and Gauss KA. Structure and regulation of the neutrophil respiratory burst oxidase: comparison with nonphagocyte oxidases. J Leukoc Biol 76: 760-781, 2004.
123. Sundaresan M, Yu ZX, Ferrans VJ, Sulciner DJ, Gutkind JS, Irani K, Goldschmidt-Clermont PJ, and Finkel T. Regulation of reactive-oxygen-species generation in fibroblasts by Rac1. Biochem J 318: 379-382, 1996.
124. Kim KS, Takeda K, Sethi R, Pracyk JB, Tanaka K, Zhou YF, Yu ZX, Ferrans VJ, Bruder JT, Kovesdi I, Irani K, Goldschmidt-Clermont P, and Finkel T. Protection from reoxygenation injury by inhibition of rac1. J Clin Invest 101: 1821-1826, 1998.
125. Kawahara T, Kohjima M, Kuwano Y, Mino H, Teshima-Kondo S, Takeya R, Tsunawaki S, Wada A, Sumimoto H, and Rokutan K. Helicobacter pylori lipopolysaccharide activates Rac1 and transcription of NADPH oxidase Nox1 and its organizer NOXO1 in guinea pig gastric mucosal cells. Am J Physiol Cell Physiol 288: C450-C457, 2005.
126. 2. Mol Cell Biol 24: 4384-4394, 2004.
127. Takeya R, Ueno N, Kami K, Taura M, Kohjima M, Izaki T, Nunoi H, and Sumimoto H. Novel human homologues of p47phox and p67phox participate in activation of superoxide-producing NADPH oxidases. J Biol Chem 278: 25234-25246, 2003.
128. Carlyon JA, Chan WT, Galan J, Roos D, and Fikrig E. Repression of rac2 mRNA expression by Anaplasma phagocytophila is essential to the inhibition of superoxide production and bacterial proliferation. J Immunol 169: 7009-7018, 2002.