Interactions between the components of the human NADPH oxidase: Intrigues in the phox family

Journal of Laboratory and Clinical Medicine

Volumn 128, Issue 5, 1996, Pages 461-476

  Leusen, Jeanette H W ^a   Verhoeven, Arthur J ^a   Roos, Dirk ^a  

^a Dept of Exp Immunohematology ^*

Author keywords

[No Author keywords available]

Indexed keywords

EID: 0030282186     PISSN: 00222143     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0022-2143(96)90043-8     Document Type: Review

References (158)

1. Weiss SJ. Tissue destruction by neutrophils. N Engl J Med 1989;320:365-76.
2. Verhoeven AJ, Bolscher BGJM, Roos D. The superoxide-generating enzyme in phagocytes: physiology, protein composition, and mechanism of activation. In: Membrane lipid oxidation. Vigo-Pelfrey C, editor. Boston: CRC press, 1991: 42-59.
3. Clark RA. The human neutrophil respiratory burst oxidase. J Infect Dis 1990;161:1140-7.
4. Williams LT, Snyderman R, Pike MC, Lefkowitz RJ. Specific receptor sites for chemotactic peptides on human polymorphonuclear leukocytes. Proc Natl Acad Sci USA 1977; 74:1204-8.
5. Lehmeyer JE, Snyderman R, Johnston RB. Stimulation of neutrophil oxidative metabolism by chemotactic peptides: influence of calcium ion concentration and cytochalasin B and comparison with stimulation by phorbol myristate acetate. Blood 1979;54:35-45.
6. --forming NADPH oxidase of the phagocytes: nature, mechanisms of activation and function. Biochim Biophys Acta 1986;853:65-89.
7. Cross AR, Jones OT. Enzymic mechanisms of superoxide production. Biochim Biophys Acta 1991;1057:281-98.
8. Morel F, Doussière J, Vignais PV. The superoxide-generating oxidase of phagocytic cells. Physiological, molecular and pathological aspects. Eur J Biochem 1991;201:523-46.
9. Baggiolini M, Boulay F, Badwey JA, Curnutte JT. Activation of neutrophil leukocytes: chemoattractant receptors and respiratory burst. FASEB J 1993;7:1004-10.
10. Quie PG, White JG, Holmes PG, Good RA. In vitro bactericidal capacity of human polymorphonuclear leucocytes: diminished activity in chronic granulomatous disease of childhood. J Clin Invest 1967;46:668-79.
11. Segal AW. Chronic granulomatous disease. Clin Exp Allergy 1991;21(suppl 1):195-8.
12. Forrest CB, Forehand JR, Axtell RA, Roberts RL, Johnston RB. Clinical features and current management of chronic granulomatous disease. Hematol Oncol Clin North Am 1988;2:253-67.
13. Smith RM, Curnutte JT. Molecular basis of chronic granulomatous disease. Blood 1991;77:673-86.
14. Kunkel LM, Monaco AP, Middlesworth W, Ochs HD, Latt SA. Specific cloning of DNA fragments absent from the DNA of a male patient with an X chromosome deletion. Proc Natl Acad Sci USA 1985;82:4778-82.
15. Dinauer MC, Pierce EA, Bruns GA, Curnutte JT, Orkin SH. Human neutrophil cytochrome b light chain (p22-phox). Gene structure, chromosomal location, and mutations in cytochrome-negative autosomal recessive chronic granulomatous disease. J Clin Invest 1990;86:1729-37.
16. Volpp BD, Nauseef WM, Clark RA. Two cytosolic neutrophil oxidase components absent in autosomal chronic granulomatous disease. Science 1988;242:1295-7.
17. Nunoi H, Rotrosen D, Gallin JI, Malech HL. Two forms of autosomal chronic granulomatous disease lack distinct neutrophil cytosol factors. Science 1988;242:1298-301.
18. Lomax KJ, Leto TL, Nunoi H, Gallin JI, Malech HL. Recombinant 47-kilodalton cytosol factor restores NADPH oxidase in chronic granulomatous disease [erratum appeared in Science 1989;246:987]. Science 1989;245:409-12.
19. Volpp BD, Nauseef WM, Donelson JE, Moser DR, Clark RA. Cloning of the cDNA and functional expression of the 47-kilodalton cytosolic component of human neutrophil respiratory burst oxidase [erratum appeared in Proc Natl Acad Sci USA 1989;86:9563]. Proc Natl Acad Sci USA 1990;86:7195-9.
20. Leto TL, Lomax KJ, Volpp BD, Nunoi H, Sechler JM, Nauseef WM, et al. Cloning of a 67-kd neutrophil oxidase factor with similarity to a noncatalytic region of p60c-src. Science 1990;248:727-30.
21. 2 oxidoreductase in human neutrophils after stimulation with phorbol myristate acetate [erratum appeared in J Biol Chem 1990;265:19370-19371]. J Biol Chem 1990;265:924-30.
22. Clark RA, Volpp BD, Leidal KG, Nauseef WM. Two cytosolic components of the human neutrophil respiratory burst oxidase translocate to the plasma membrane during cell activation. J Clin Invest 1990;85:714-21.
23. -245 subunits from neutrophils in X-linked chronic granulomatous disease. Nature 1987;326:88-91.
24. Parkos CA, Allen RA, Cochrane CG, Jesaitis AJ. Purified cytochrome b from human plasma membrane is comprised of two polypeptides with relative molecular weights of 91,000 and 22,000. J Clin Invest 1987;80:732-42.
25. Segal AW, Jones OT. Subcellular distribution and some properties of the cytochrome b component of the microbicidal oxidase system of human neutrophils. Biochem J 1979; 182:181-8.
26. Cross AR, Jones TG, Harper AM, Segal AW. Oxidation-reduction properties of the cytochrome b found in the plasma-membrane fraction of human neutrophils. Biochem J 1981;194:599-606.
27. -245 is a flavocytochrome containing FAD and the NADPH-binding site of the microbicidal oxidase of phagocytes. Biochem J 1992;284:781-8.
28. 558: the flavin-binding component of the phagocyte NADPH oxidase. Science 1992;256:1459-62.
29. 558, a component of the phagocyte NADPH oxidase, is a flavoprotein. Biochem Biophys Res Commun 1992;186:1368-75.
30. Quinn MT, Mullen ML, Jesaitis AJ. Human neutrophil cytochrome b contains multiple hemes. Evidence for heme associated with both subunits. J Biol Chem 1992;267:7303-9.
31. Segal AW. The electron transport chain of the microbicidal oxidase of phagocytic cells and its involvement in the molecular pathology of chronic granulomatous disease. J Clin Invest 1989;83:1785-93.
32. 559 in human neutrophils [erratum appeared in Eur J Haematol 1989;8:270]. Eur J Haematol 1989;43:67-77.
33. 558 in human blood phagocytes by immunoelectron microscopy. Blood 1990;76:2105-16.
34. 558 and the adhesion molecule CD11b/CD18. Blood 1993;81:3122-9.
35. Borregaard N, Heiple JM, Simons ER, Clark RA. Subcellular localization of the b-cytochrome component of the human neutrophil microbicidal oxidase: translocation during activation. J Cell Biol 1983;97:52-61.
36. Royer-Pokora B, Kunkel LM, Monaco AP, Goff SC, Newburger PE, Baehner RL, et al. Cloning the gene for an inherited human disorder-chronic granulomatous disease-on the basis of its chromosomal location. Nature 1986; 322:32-8.
37. -245. Nature 1987;327:720-1.
38. Parkos CA, Dinauer MC, Walker LE, Allen RA, Jesaitis AJ, Orkin SH. Primary structure and unique expression of the 22-kilodalton light chain of human neutrophil cytochrome b. Proc Natl Acad Sci USA 1988;85:3319-23.
39. Dinauer MC, Orkin SH, Brown R, Jesaitis AJ, Parkos CA. The glycoprotein encoded by the X-linked chronic granulomatous disease locus is a component of the neutrophil cytochrome b complex. Nature 1987;327:717-20.
40. 558 in neutrophil membrane analyzed by anti-peptide antibodies and proteolysis. J Biol Chem 1992;267:180-4.
41. 558-negative form of the disease. J Leukoc Biol 1992;51:164-71.
42. Dinauer MC, Curnutte JT, Rosen H, Orkin SH. A missense mutation in the neutrophil cytochrome b heavy chain in cytochrome-positive X-linked chronic granulomatous disease. J Clin Invest 1989;84:2012-6.
43. Schapiro BL, Newburger PE, Klempner MS, Dinauer MC. Chronic granulomatous disease presenting in a 69-year-old man. N Engl J Med 1991;325:1786-90.
44. 558 of the human NADPH oxidase leading to defective translocation of the cytosolic proteins p47-phox and p67-phox. J Clin Invest 1994;93:2120-6.
45. 558 light chain of the NADPH oxidase (p22-phox). Am J Hum Genet 1992;51:1127-35.
46. Dinauer MC, Pierce EA, Erickson RW, Muhlebach TJ, Messner H, Orkin SH, et al. Point mutation in the cytoplasmic domain of the neutrophil p22-phox cytochrome b subunit is associated with a nonfunctional NADPH oxidase and chronic granulomatous disease. Proc Natl Acad Sci USA 1991;88:11231-5.
47. Koch CA, Anderson D, Moran MF, Ellis C, Pawson T. SH2 and SH3 domains: elements that control interactions of cytoplasmic signaling proteins. Science 1991;252:668-74.
48. Musacchio A, Gibson T, Lehto VP, Saraste M. SH3: an abundant protein domain in search of a function. FEBS Lett 1992;307:55-61.
49. Ren R, Mayer BJ, Cicchetti P, Baltimore D. Identification of a ten-amino acid proline-rich SH3 binding site. Science 1993;259:1157-61.
50. 558 of the human NADPH oxidase (p22-phox) leads to defective translocation of the cytosolic proteins p47-phox and p67-phox. J Exp Med 1994; 180:2329-34.
51. Parkos CA, Dinauer MC, Jesaitis AJ, Orkin SH, Curnutte JT. Absence of both the 91kd and 22kd subunits of human neutrophil cytochrome b in two genetic forms of chronic granulomatous disease. Blood 1989;73:1416-20.
52. 558 of human neutrophils. Blood 1989;73:1686-94.
53. Porter CD, Parkar MH, Verhoeven AJ, Levinsky RJ, Collins MKL, Kinnon C. p22-phox-Deficient chronic granulomatous disease: reconstitution by retrovirus-mediated expression and identification of a biosynthetic intermediate of gp91-phox. Blood 1994;84:2767-75.
54. Quinn MT, Parkos CA, Walker L, Orkin SH, Dinauer MC, Jesaitis AJ. Association of a Ras-related protein with cytochrome b of human neutrophils. Nature 1989;342:198-200.
55. 559. Blood 1992;79:1563-73.
56. Quilliam LA, Mueller H, Bohl BP, Prossnitz V, Sklar LA, Der CJ, et al. Rap1A is a substrate for cyclic AMP-dependent protein kinase in human neutrophils [erratum appeared in J Immunol 1991;147:3660]. J Immunol 1991;147: 1628-35.
57. Bokoch GM, Quilliam LA, Bohl BP, Jesaitis AJ, Quinn MT. Inhibition of Rap1A binding to cytochrome b558 of NADPH oxidase by phosphorylation of Rap1A. Science 1991;254:1794-6.
58. Clark RA, Malech HL, Gallin JI, Nunoi H, Volpp BD, Pearson DW, et al. Genetic variants of chronic granulomatous disease: prevalence of deficiencies of two cytosolic components of the NADPH oxidase system. N Engl J Med 1989;321:647-52.
59. Segal AW, Heyworth PG, Cockcroft S, Barrowman MM. Stimulated neutrophils from patients with autososomal recessive chronic granulomatous disease fail to phosphorylate a Mr-44,000 protein. Nature 1985;316:547-9.
60. Andrews PC, Babior BM. Phosphorylation of cytosolic proteins by resting and activated human neutrophils. Blood 1984;64:883-90.
61. Hayakawa T, Suzuki K, Suzuki S, Andrews PC, Babior BM. A possible role for protein phosphorylation in the activation of the respiratory burst in human neutrophils. Evidence from studies with cells from patients with chronic granulomatous disease. J Biol Chem 1986;261:9109-15.
62. Heyworth PG, Shrimpton CF, Segal AW. Localization of the 47 kd phosphoprotein involved in the respiratory-burst NADPH oxidase of phagocytic cells. Biochem J 1989;260: 243-8.
63. Okamura N, Curnutte JT, Roberts RL, Babior BM. Relationship of protein phosphorylation to the activation of the respiratory burst in human neutrophils. Defects in the phosphorylation of a group of closely related 48-kd proteins in two forms of chronic granulomatous disease. J Biol Chem 1988;263:6777-82.
64. Okamura N, Malawista SE, Roberts RL, Rosen H, Ochs HD, Babior BM, et al. Phosphorylation of the oxidase-related 48K phosphoprotein family in the unusual autosomal cytochrome-negative and X-linked cytochrome-positive types of chronic granulomatous disease. Blood 1988;72:811-6.
65. Francke U, Hsieh CL, Foellmer BE, Lomax KJ, Malech HL, Leto TL. Genes for two autosomal recessive forms of chronic granulomatous disease assigned to 1q25 (NCF2) and 7q11.23 (NCF1). Am J Hum Genet 1990;47:483-92.
66. Curnutte JT, Scott PJ, Mayo LA. Cytosolic components of the respiratory burst oxidase: resolution of four components, two of which are missing in complementing types of chronic granulomatous disease. Proc Natl Acad Sci USA 1989;86:825-9.
67. Bolscher BGJM, van Zwieten R, Kramer IM, Weening RS, Verhoeven AJ, Roos D. 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. J Clin Invest 1989;83:757-63.
68. Teahan CG, Totty N, Casimir CM, Segal AW. Purification of the 47 kd phosphoprotein associated with the NADPH oxidase of human neutrophils. Biochem J 1990;267:485-9.
69. 558. J Clin Invest 1991; 87:352-6.
70. 558 91-kilodalton subunit functional domain: identification of peptide sequence and amino acids essential for activity. Biochemistry 1992;31: 2686-90.
71. Uhlinger DJ, Taylor KL, Lambeth JD. p67-phox enhances the binding of p47-phox to the human neutrophil respiratory burst oxidase complex. J Biol Chem 1994;269:22095-8.
72. Wientjes FB, Hsuan JJ, Totty NF, Segal AW. p40phox, a third cytosolic component of the activation complex of the NADPH oxidase to contain src homology 3 domains. Biochem J 1993;296:557-61.
73. Tsunawaki S, Mizunari H, Nagata M, Tatsuzawa O, Kuratsuji T. A novel cytosolic component, p40phox, of respiratory burst oxidase associates with p67phox and is absent in patients with chronic granulomatous disease who lack p67phox. Biochem Biophys Res Commun 1994;199:1378-87.
74. Knaus UG, Heyworth PG, Evans T, Curnutte JT, Bokoch GM. Regulation of phagocyte oxygen radical production by the GTP-binding protein Rac 2. Science 1991;254:1512-5.
75. rac1. Nature 1991;353:668-70.
76. Abo A, Pick E. Purification and characterization of a third cytosolic component of the superoxide-generating NADPH oxidase of macrophages. J Biol Chem 1991;266:23577-85.
77. Knaus UG, Heyworth PG, Kinsella BT, Curnutte JT, Bokoch GM. Purification and characterization of Rac 2. A cytosolic GTP-binding protein that regulates human neutrophil NADPH oxidase. J Biol Chem 1992;267:23575-82.
78. Dorseuil O, Vazquez A, Lang P, Bertoglio J, Gacon G, Leca G. Inhibition of superoxide production in B lymphocytes by rac antisense oligonucleotides. J Biol Chem 1992;267:20540-2.
79. phox is required for the translocation of rac 1 but not of rac 2 from cytosol to the membranes. Biochem J 1995;308:991-4.
80. Mizuno T, Kaibuchi K, Ando S, Musha T, Hiraoka K, Takaishi K, et al. 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 1992;267:10215-8.
81. Heyneman RA, Vercauteren RE. Activation of a NADPH oxidase from horse polymorphonuclear leukocytes in a cell-free system. J Leukocyte Biol 1984;36:751-9.
82. Bromberg Y, Pick E. Activation of NADPH-dependent superoxide production in a cell-free system by sodium dodecyl sulfate. J Biol Chem 1985;260:13539-45.
83. Curnutte JT. Activation of human neutrophil nicotinamide adenine dinucleotide phosphate, reduced (trisphosphopyridine nucleotide, reduced) oxidase by arachidonic acid in a cell-free system. J Clin Invest 1985;75:1740-3.
84. Gabig TG, English D, Akard LP, Schell MJ. Regulation of neutrophil NADPH oxidase activation in a cell-free system by guanine nucleotides and fluoride. Evidence for participation of a pertussis and cholera toxin-insensitive G protein. J Biol Chem 1987;262:1685-90.
85. Clark RA, Leidal KG, Pearson DW, Nauseef WM. NADPH oxidase of human neutrophils. Subcellular localization and characterization of an arachidonate-activatable superoxide-generating system. J Biol Chem 1987;262:4065-74.
86. Caldwell SE, McCall CE, Hendricks CL, Leone PA, Bass DA, McPhail LC. Coregulation of NADPH oxidase activation and phosphorylation of a 48-kd protein(s) by a cytosolic factor defective in autosomal recessive chronic granulomatous disease. J Clin Invest 1988;81:1485-96.
87. Doussière J, Pilloud MC, Vignais PV. Activation of bovine neutrophil oxidase in a cell free system. GTP-dependent formation of a complex between a cytosolic factor and a membrane protein. Biochem Biophys Res Commun 1988; 152:993-1001.
88. Bolscher BGJM, Denis SW, Verhoeven AJ, Roos D. The activity of one soluble component of the cell-free NADPH:O2 oxidoreductase of human neutrophils depends on guanosine 5′-O-(3-thio)triphosphate. J Biol Chem 1990;265: 15782-7.
89. -245. J Biol Chem 1992;267:16767-70.
90. 559 in the absence of cytosolic activators. FEBS Lett 1993;327:57-62.
91. 559. Mechanism of cytosol-independent activation. FEBS Lett 1994;338:285-9.
92. 558. J Biol Chem 1991;266:1627-34.
93. +) with partially functional cytochrome b. J Biol Chem 1995; 270:8194-200.
94. -245 of the neutrophil superoxide-generating system contains two non-identical hemes. J Biol Chem 1995;270:17075-7.
95. Azuma H, Oomi H, Sasaki K, Kawabata I, Sakaino T, Koyano S, et al. A new mutation in exon 12 of the gp91-phox gene leading to cytochrome b-positive X-linked chronic granulomatous disease. Blood 1995;85:3274-7.
96. -245 beta-chain. Protein Sci 1993;2:1675-85.
97. Verhoeven AJ, Leusen JHW, Kessels GCR, Hilarius PM, De Bont DB, Liskamp RM. Inhibition of neutrophil NADPH oxidase assembly by a myristoylated pseudosubstrate of protein kinase C. J Biol Chem 1993;268:18593-8.
98. Cross AR, Yarchover JL, Curnutte JT. The superoxide-generating system of human neutrophils possesses a novel diaphorase activity. Evidence for distinct regulation of electron flow within NADPH oxidase by p67-phox and p47-phox. J Biol Chem 1994;269:21448-54.
99. phox have distinct roles in the regulation of electron flow in NADPH oxidase. J Biol Chem 1995;270: 6543-8.
100. --generating system in neutrophils. J Biol Chem 1992;267:19072-4.
101. DeLeo FR, Yu L, Burritt JB, Loetterle LR, Bond CW, Jesaitis AJ, et al. Mapping sites of interaction of p47-phox and flavocytochrome b with random sequence peptide phage display libraries. Proc Natl Acad Sci USA 1995;92: 7110-4.
102. 558. J Biol Chem 1995;270: 26246-51.
103. Joseph G, Gorzalczany Y, Koshkin V, Pick E. Inhibition of NADPH oxidase activation by synthetic peptides mapping within the carboxyl-terminal domain of small GTP-binding proteins. Lack of amino acid sequence specificity and importance of polybasic motif. J Biol Chem 1994;269:29024-31.
104. Park JW, Ma M, Ruedi JM, Smith RM, Babior BM. The cytosolic components of the respiratory burst oxidase exist as a M(r) approximately 240,000 complex that acquires a membrane-binding site during activation of the oxidase in a cell-free system. J Biol Chem 1992;267:17327-32.
105. Park JW, El Benna J, Scott KE, Christensen BL, Chanock SJ, Babior BM. Isolation of a complex of respiratory burst oxidase components from resting neutrophil cytosol. Biochemistry 1994;33:2907-11.
106. Iyer SS, Pearson DW, Nauseef WM, Clark RA. Evidence for a readily dissociable complex of p47phox and p67phox in cytosol of unstimulated human neutrophils. J Biol Chem 1994;269:22405-11.
107. Pawson T. SH2 and SH3 domains in signal transduction. Adv Cancer Res 1994;64:87-110.
108. phox of the human neutrophil NADPH oxidase that are not required for activation in the cell-free system. J Biol Chem 1995;270:11216-21.
109. Uhlinger DJ, Perry DK. A carboxy-terminal peptide from p47-phox is a substrate for phosphorylation by protein kinase C and by a neutrophil protein kinase. Biochem Biophys Res Commun 1992;187:940-8.
110. Finan P, Shimizu Y, Gout I, Hsuan J, Truong O, Butcher C, et al. An SH3 domain and proline-rich sequence mediate an interaction between two components of the phagocyte NADPH oxidase complex. J Biol Chem 1994;269:13752-5.
111. Leto TL, Adams AG, de Mendez I. Assembly of the phagocyte NADPH oxidase: binding of Src homology 3 domains to proline-rich targets. Proc Natl Acad Sci USA 1994;91: 10650-4.
112. Sumimoto H, Kage Y, Nunoi H, Sasaki H, Nose T, Fukumaki Y, et al. Role of Src homology 3 domains in assembly and activation of the phagocyte NADPH oxidase. Proc Natl Acad Sci USA 1994;91:5345-9.
113. de Mendez I, Garrett MC, Adams AG, Leto TL. Role of p67-phox SH3 domains in assembly of the NADPH oxidase system. J Biol Chem 1994;269:16326-32.
114. phox of the neutrophil oxidase complex using the two-hybrid system. J Biol Chem 1995;270:5695-7.
115. Kramer IJM, Verhoeven AJ, van der Bend RL, Weening RS, Roos D. Purified protein kinase C phosphorylates a 47-kd protein in control neutrophil cytoplasts but not in neutrophil cytoplasts from patients with the autosomal form of chronic granulomatous disease. J Biol Chem 1988;263: 2352-7.
116. Nauseef WM, Volpp BD, McCormick S, Leidal KG, Clark RA. Assembly of the neutrophil respiratory burst oxidase. Protein kinase C promotes cytoskeletal and membrane association of cytosolic oxidase components. J Biol Chem 1991;266:5911-7.
117. Curnutte JT, Erickson RW, Ding J, Badwey JA. Reciprocal interactions between protein kinase C and components of the NADPH oxidase complex may regulate superoxide production by neutrophils stimulated with a phorbol ester. J Biol Chem 1994;269:10813-9.
118. Kramer IJM, van der Bend RL, Tool ATJ, van Blitterswijk WJ, Roos D, Verhoeven AJ. 1-O-hexadecyl-2-O-methylglycerol, a novel inhibitor of protein kinase C, inhibits the respiratory burst in human neutrophils. J Biol Chem 1989; 10:5876-84.
119. Robinson JM, Heyworth PG, Badway JA. Utility of staurosporine in uncovering differences in the signal transduction pathways for superoxide production in neutrophils. Biochim Biophys Acta 1990;1055:55-62.
120. Kessels GC, Krause, KH, Verhoeven, AJ. Protein kinase C activity is not involved in N-formylmethionyl-leucyl-phenylalanine-induced phospholipase D activation in human neutrophils but is essential for concomitant NADPH oxidase activation: studies with a staurosporine analogue with improved selectivity for protein kinase C. Biochem J 1993;292: 781-5.
121. Rotrosen D, Leto TL. Phosphorylation of neutrophil 47-kd cytosolic factor. Translocation to membrane is associated with distinct phosphorylation events. J Biol Chem 1990;265: 19910-5.
122. El Benna J, Faust LP, Babior BM. The phosphorylation of the respiratory burst oxidase component p47phox during neutrophil activation. Phosphorylation of sites recognized by protein kinase C and by proline-directed kinases. J Biol Chem 1994;269:23431-6.
123. Heyworth PG, Badwey JA. Continuous phosphorylation of both the 47 and the 49 kd proteins occurs during superoxide production by neutrophils. Biochim Biophys Acta 1990; 1052:299-305.
124. Ding J, Badwey JA. Effects of antagonists of protein phosphatases on superoxide release by neutrophils. J Biol Chem 1992;267:6442-8.
125. Robinson JM, Badwey JA. The NADPH oxidase complex of phagocytic leukocytes: a biochemical and cytochemical view. Histochemistry 1995;103:163-80.
126. Lu DJ, Takai A, Leto TL, Grinstein S. Modulation of neutrophil activation by okadaic acid, a protein phosphatase inhibitor. Am J Physiol 1992;262:C39-49.
127. Ding J, Badwey JA. Stimulation of neutrophils with a chemoattractant activates several novel protein kinases that can catalyze the phosphorylation of peptides derived from the 47-kd protein component of the phagocyte oxidase and myristoylated alanine-rich C kinase substrate. J Biol Chem 1993;268:17326-33.
128. Grinstein S, Furuya W, Butler JR, Tseng J. Receptor-mediated activation of multiple serine/threonine kinases in human leukocytes. J Biol Chem 1993;268:20223-31.
129. Ding J, Badwey JA. Wortmannin and 1-butanol block activation of a novel family of protein kinases in neutrophils. FEBS Lett 1994;348:149-52.
130. Gonzales FA, Raden DL, Davis RJ. Identification of substrate recognition determinants for human ERK1 and ERK2 protein kinases. J Biol Chem 1991;266:22159-63.
131. Kennely PJ, Krebs EG. Consensus sequences as substrate specificity determinants for protein kinases and protein phosphatases. J Biol Chem 1991;266:15555-8.
132. Jackson SH, Malech HL, Kozak CA, Lomax KJ, Gallin JI, Holland SM. Cloning and functional expression of the mouse homologue of p47phox. Immunogenetics 1994;39: 272-5
133. phox, a subunit of the respiratory burst oxidase. Functions of the individual target serines as evaluated by site-directed mutagenesis. J Clin Invest 1995; 96:1499-505.
134. Kwong CH, Malech HL, Rotrosen D, Leto TL. Regulation of the human neutrophil NADPH oxidase by rho-related G-proteins. Biochemistry 1993;32:5711-7.
135. Heyworth PG, Knaus UG, Xu X, Uhlinger DJ, Conroy L, Bokoch GM, et al. Requirement for posttranslational processing of Rac GTP-binding proteins for activation of human neutrophil NADPH oxidase. Mol Biol Cell 1993;4: 261-9.
136. Ando S, Kaibuchi K, Sasaki T, Hiraoka K, Nishiyama T, Mizuno T, et al. 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. J Biol Chem 1995;36:25709-13.
137. Maly FE, Quilliam LA, Dorseuil O, Der CJ, Bokoch GM. Activated or dominant inhibitory mutants of Rap1A decrease the oxidative burst of Epstein-Barr virus-transformed human B lymphocytes. J Biol Chem 1994;269:18743-6.
138. Gabig TG, Crean CD, Mantel PL, Rosli R. Function of wild-type or mutant Rac2 and Rap1a GTPases in differentiated HL60 cell NADPH oxidase activation. Blood 1995; 85:804-11.
139. Chuang TH, Bohl BP, Bokoch GM. Biologically active lipids are regulators of Rac.GDI complexation. J Biol Chem 1993; 268:26206-11.
140. Bourmeyster N, Stasia M-J, Garin J, Gagon J, Boquet P, Vignais PV. Copurification of Rho protein and the Rho-GDP dissociation inhibitor from bovine neutrophil cytosol. Effect of phosphoinositides on Rho ADP-ribosylation by the C3 exoenzyme of Clostridium botulinium. Biochemistry 1992;31:12863-9.
141. Hawkins PT, Eguinoa A, Qiu R-G, Stokoe D, Cooke FT, Walters R, et al. PDGF stimulates an increase in GTP-Rac via activation of phosphoinositide 3-kinase. Curr Biol 1995; 5:393-403.
142. Dewald B, Thelen M, Baggiolini M. Two transduction sequences are necessary for neutrophil activation by receptor agonists. J Biol Chem 1988;263:16179-84.
143. Okada T, Sakuma L, Fukui Y, Hazeki O, Ui M. Blockage of chemotactic peptide-induced stimulation of neutrophils by wortmannin as a result of selective inhibition of phosphatidylinositol 3-kinase. J Biol Chem 1994;269:3563-7.
144. Diekmann D, Abo A, Johnston C, Segal AW, Hall A. Interaction of Rac with p67phox and regulation of phagocytic NADPH oxidase activity. Science 1994;265:531-3.
145. phox are targets for cdc42Hs and Rac1 in neutrophils. J Biol Chem 1995;270:10717-22.
146. Knaus UG, Morris S, Dong H-J, Chernoff J, Bokoch GM. Regulation of human leukocyte p21-activated kinases through G protein-coupled receptors. Science 1995;269:221-3.
147. White JR, Naccache PH, Sha'afi RI. Stimulation by chemotactic factor of actin association with the cytoskeleton in rabbit neutrophils. J Biol Chem 1983;258:14041-7.
148. Quinn MT, Evans T, Loetterle LR, Jesaitis AJ, Bokoch GM. Translocation of Rac correlates with NADPH oxidase activation. Evidence for equimolar translocation of oxidase components. J Biol Chem 1993;268:20983-7.
149. El Benna J, Ruedi JM, Babior BM. Cytosolic guanine nucleotide-binding protein Rac2 operates in vivo as a component of the neutrophil respiratory burst oxidase. Transfer of Rac2 and the cytosolic oxidase components p47phox and p67phox to the submembranous actin cytoskeleton during oxidase activation. J Biol Chem 1994;269:6729-34.
150. Le Cabec V, Möhn H, Gacon G, Maridonneau-Parini I. The small GTP-binding protein rac is not recruited to the plasma membrane upon NADPH oxidase activation in human neutrophils. Biochem Biophys Res Commun 1994;198:1216-24.
151. 558. J Biol Chem 1994;269: 30749-52.
152. Dorseuil O, Quinn MT, Bokoch GM. Dissociation of rac translocation from p47phox/p67phox movements in human neutrophils by tyrosine kinase inhibitors. J Leukoc Biol 1995;58:108-13.
153. Ridley AJ, Paterson HF, Johnston CL, Diekmann D, Hall A. The small GTP-binding protein rac regulates growth factor-induced membrane ruffling. Cell 1992;70:401-10.
154. Akard LP, English D, Gabig TG. Rapid deactivation of NADPH oxidase in neutrophils: continuous replacement by newly activated enzyme sustains the respiratory burst. Blood 1988;72:322-7.
155. 558 inhibit superoxide generation in a cell-free system from human neutrophils. Biochem Biophys Res Commun 1994;204:924-9.
156. Tisch D, Sharoni Y, Danilenko M, Aviram I. The assembly of neutrophil NADPH oxidase: effect of mastoparan and its synthetic analogues. Biochem J 1995;310:715-9.
157. Karplus PA, Daniels MJ, Herriott JR. Atomic structure of
158. Kraulis P. A program to produce both detailed and schematic plots of protein structures. J Appl Cryst 1991;24:946-50.