Current molecular models for NADPH oxidase regulation by Rac GTPase.

Reactive oxygen species (ROS) have been increasingly recognized as important components of cell signaling in addition to their well-established roles in host defense. The formation of ROS in phagocytic and nonphagocytic cells involves membrane-localized and Rac guanosine triphosphatase (GTPase)-regulated reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase(s). We discuss here the current molecular models for Rac GTPase action in the control of the phagocytic leukocyte NADPH oxidase. As a mechanistically detailed example of Rac GTPase signaling, the NADPH oxidase provides a potential paradigm for signaling by Rho family GTPases in general.

[1]  G. Bokoch,et al.  CHAPTER 238 – Regulation of the NADPH Oxidase by Rac GTPase , 2003 .

[2]  N. Shenoy,et al.  Inhibition of constitutively active forms of mutant kit by multitargeted indolinone tyrosine kinase inhibitors. , 2002, Blood.

[3]  N. Sigal,et al.  A Prenylated p67 phox -Rac1 Chimera Elicits NADPH-dependent Superoxide Production by Phagocyte Membranes in the Absence of an Activator and of p47 phox , 2002, The Journal of Biological Chemistry.

[4]  M. Dinauer,et al.  Rac Activation Induces NADPH Oxidase Activity in Transgenic COS phox Cells, and the Level of Superoxide Production Is Exchange Factor-dependent* , 2002, The Journal of Biological Chemistry.

[5]  J. Lambeth Nox/Duox family of nicotinamide adenine dinucleotide (phosphate) oxidases , 2002, Current opinion in hematology.

[6]  N. Sigal,et al.  Activation of the superoxide-generating NADPH oxidase by chimeric proteins consisting of segments of the cytosolic component p67(phox) and the small GTPase Rac1. , 2001, Biochemistry.

[7]  S. Grizot,et al.  Mechanism of NADPH oxidase activation by the Rac/Rho-GDI complex. , 2001, Biochemistry.

[8]  Paul Tempst,et al.  PtdIns(3)P regulates the neutrophil oxidase complex by binding to the PX domain of p40phox , 2001, Nature Cell Biology.

[9]  S. Grizot,et al.  The Active N-terminal Region of p67 phox , 2001, The Journal of Biological Chemistry.

[10]  S. Grizot,et al.  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. , 2001, The Journal of biological chemistry.

[11]  C. Der,et al.  The Insert Region of Rac1 Is Essential for Membrane Ruffling but Not Cellular Transformation , 2001, Molecular and Cellular Biology.

[12]  G. Bokoch,et al.  Molecular basis for Rac2 regulation of phagocyte NADPH oxidase , 2001, Nature Immunology.

[13]  N. Sigal,et al.  Targeting of Rac1 to the Phagocyte Membrane Is Sufficient for the Induction of NADPH Oxidase Assembly* , 2000, The Journal of Biological Chemistry.

[14]  S. Smerdon,et al.  Structure of the TPR domain of p67phox in complex with Rac.GTP. , 2000, Molecular cell.

[15]  Gregory R. Hoffman,et al.  Structure of the Rho Family GTP-Binding Protein Cdc42 in Complex with the Multifunctional Regulator RhoGDI , 2000, Cell.

[16]  K. Irani,et al.  Inhibition of the Rac1 GTPase protects against nonlethal ischemia/reperfusion‐induced necrosis and apoptosis in vivo , 2000, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[17]  古賀 博文 Tetratricopeptide repeat (TPR) motifs of p67phox participate in interaction with the small GTPase rac and activation of the phagocyte NADPH oxidase , 2000 .

[18]  J. Lambeth Regulation of the Phagocyte Respiratory Burst Oxidase by Protein Interactions , 2000 .

[19]  F. Inagaki,et al.  Tetratricopeptide Repeat (TPR) Motifs of p67 phox Participate in Interaction with the Small GTPase Rac and Activation of the Phagocyte NADPH Oxidase* , 1999, The Journal of Biological Chemistry.

[20]  J. Lambeth,et al.  The p67 phox Activation Domain Regulates Electron Flow from NADPH to Flavin in Flavocytochromeb 558 * , 1999, The Journal of Biological Chemistry.

[21]  A. Cross,et al.  Simultaneous Presence of p47 phox and Flavocytochrome b −245 Are Required for the Activation of NADPH Oxidase by Anionic Amphiphiles , 1999, The Journal of Biological Chemistry.

[22]  B. Babior NADPH oxidase: an update. , 1999, Blood.

[23]  D. Williams,et al.  Deficiency of the hematopoietic cell-specific Rho family GTPase Rac2 is characterized by abnormalities in neutrophil function and host defense. , 1999, Immunity.

[24]  D. Bar-Sagi,et al.  A Rac1 Effector Site Controlling Mitogenesis through Superoxide Production* , 1998, The Journal of Biological Chemistry.

[25]  J. Lambeth,et al.  Regulation of the Neutrophil Respiratory Burst Oxidase , 1998, The Journal of Biological Chemistry.

[26]  A. Toporik,et al.  Mutational analysis of novel effector domains in Rac1 involved in the activation of nicotinamide adenine dinucleotide phosphate (reduced) oxidase. , 1998, Biochemistry.

[27]  V. Ferrans,et al.  Protection from reoxygenation injury by inhibition of rac1. , 1998, The Journal of clinical investigation.

[28]  J. Zweier,et al.  Mitogenic Signaling Mediated by Oxidants in Ras-Transformed Fibroblasts , 1997, Science.

[29]  F. DeLeo,et al.  Assembly of the phagocyte NADPH oxidase: molecular interaction of oxidase proteins , 1996, Journal of leukocyte biology.

[30]  V. Koshkin,et al.  The Cytosolic Component p47phox Is Not a Sine Qua Non Participant in the Activation of NADPH Oxidase but Is Required for Optimal Superoxide Production* , 1996, The Journal of Biological Chemistry.

[31]  J. Lambeth,et al.  NADPH Oxidase Activity Is Independent of p47phox in Vitro* , 1996, The Journal of Biological Chemistry.

[32]  V. Ferrans,et al.  Regulation of reactive-oxygen-species generation in fibroblasts by Rac1. , 1996, The Biochemical journal.

[33]  A. Abo,et al.  Rac “Insert Region” Is a Novel Effector Region That Is Implicated in the Activation of NADPH Oxidase, but Not PAK65* , 1996, The Journal of Biological Chemistry.

[34]  G. Panayotou,et al.  Interactions between cytosolic components of the NADPH oxidase: p40phox interacts with both p67phox and p47phox. , 1996, The Biochemical journal.

[35]  J. Lambeth,et al.  NADPH Oxidase Activity Is Independent of p47 in Vitro* , 1996 .

[36]  E. Pick,et al.  " Peptide Walking" Is a Novel Method for Mapping Functional Domains in Proteins , 1995, The Journal of Biological Chemistry.

[37]  G. Bokoch,et al.  Regulation of human leukocyte p21-activated kinases through G protein--coupled receptors. , 1995, Science.

[38]  G. Bokoch,et al.  Dissociation of Rac translocation from p47phox/p67phox movements in human neutrophils by tyrosine kinase inhibitors , 1995, Journal of leukocyte biology.

[39]  P. Heyworth,et al.  A Variant X-linked Chronic Granulomatous Disease Patient (X91+) with Partially Functional Cytochrome b(*) , 1995, The Journal of Biological Chemistry.

[40]  V. Kaartinen,et al.  Increased neutrophil respiratory burst in bcr-null mutants , 1995, Cell.

[41]  G. Bokoch Regulation of the phagocyte respiratory burst by small GTP-binding proteins. , 1995, Trends in cell biology.

[42]  G M Bokoch,et al.  Guanine nucleotide exchange regulates membrane translocation of Rac/Rho GTP-binding proteins. , 1994, The Journal of biological chemistry.

[43]  G. Bokoch,et al.  Rac translocates independently of the neutrophil NADPH oxidase components p47phox and p67phox. Evidence for its interaction with flavocytochrome b558. , 1994, The Journal of biological chemistry.

[44]  J. Lambeth,et al.  Ras effector-homologue region on Rac regulates protein associations in the neutrophil respiratory burst oxidase complex. , 1994, Biochemistry.

[45]  J. Settleman,et al.  Differing structural requirements for GTPase-activating protein responsiveness and NADPH oxidase activation by Rac. , 1994, The Journal of biological chemistry.

[46]  A. Abo,et al.  Interaction of Rac with p67phox and regulation of phagocytic NADPH oxidase activity. , 1994, Science.

[47]  E. Pick,et al.  The GDP-bound form of the small G protein Rac1 p21 is a potent activator of the superoxide-forming NADPH oxidase of macrophages. , 1994, The Journal of biological chemistry.

[48]  A. Jesaitis,et al.  Translocation of Rac correlates with NADPH oxidase activation. Evidence for equimolar translocation of oxidase components. , 1993, The Journal of biological chemistry.

[49]  J. Bertoglio,et al.  Inhibition of superoxide production in B lymphocytes by rac antisense oligonucleotides. , 1992, The Journal of biological chemistry.

[50]  G. Bokoch,et al.  Regulation of phagocyte oxygen radical production by the GTP-binding protein Rac 2. , 1991, Science.

[51]  A. Abo,et al.  Activation of the NADPH oxidase involves the small GTP-binding protein p21rac1 , 1991, Nature.