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The Herman B Wells Center for Pediatric Research, Department of Pediatrics (Hematology/Oncology) and Medical and Molecular Genetics, The James Whitcomb Riley Hospital for Children, Indiana University Medical Center, Indianapolis, IN 46202
Rac2 is a hematopoietic-specific Rho family GTPase implicated as an
important constituent of the NADPH oxidase complex and shares 92%
amino acid identity with the ubiquitously expressed Rac1. In bone
marrow (BM) neutrophils isolated from
rac2-/- mice generated by gene targeting,
we previously reported that PMA-induced superoxide production was
reduced by about 4-fold, which was partially corrected in
TNF-
-primed BM neutrophils and in peritoneal exudate neutrophils. We
investigated receptor-mediated activation of the NADPH oxidase in the
current study, finding that superoxide production in
rac2-/- BM and peritoneal exudate
neutrophils was normal in response to opsonized zymosan, reduced to
22% of wild type in response to IgG-coated SRBC, and almost absent in
response to fMLP. In wild-type murine BM neutrophils, phosphorylation
of extracellular signal-regulated kinase 1/2 (ERK1/2), p38
mitogen-activated protein kinase, c-Jun N-terminal kinase, and Akt was
induced by PMA or fMLP, which was decreased in
rac2-/- neutrophils for ERK1/2 and p38.
Activation of p38 by either opsonized zymosan or IgG-coated SRBC was
similar in wild-type and rac2-/- cells.
Inhibition of ERK1/2 or p38 activation using either PD98059 or
SB203580, respectively, had only a modest effect on fMLP-elicited
superoxide production and no effect on the PMA-induced response. These
data provide genetic evidence supporting an important role for Rac2 in
regulating neutrophil NADPH oxidase activation downstream of
chemoattractant and Fc
receptors. The effect of Rac2 deficiency on
superoxide production is probably exerted through multiple pathways,
including those independent of mitogen-activated protein kinase
activation.
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C. Papaharalambus, W. Sajjad, A. Syed, C. Zhang, M. O. Bergo, R. W. Alexander, and M. Ahmad Tumor Necrosis Factor {alpha} Stimulation of Rac1 Activity: ROLE OF ISOPRENYLCYSTEINE CARBOXYLMETHYLTRANSFERASE J. Biol. Chem., May 13, 2005; 280(19): 18790 - 18796. [Abstract] [Full Text] [PDF]
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Z. T. Kneass and R. B. Marchase Protein O-GlcNAc Modulates Motility-associated Signaling Intermediates in Neutrophils J. Biol. Chem., April 15, 2005; 280(15): 14579 - 14585. [Abstract] [Full Text] [PDF]
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 M. B. Fessler, S. K. Young, S. Jeyaseelan, J. G. Lieber, P. G. Arndt, J. A. Nick, and G. S. Worthen A Role for Hydroxy-Methylglutaryl Coenzyme A Reductase in Pulmonary Inflammation and Host Defense Am. J. Respir. Crit. Care Med., March 15, 2005; 171(6): 606 - 615. [Abstract] [Full Text] [PDF]
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Y. Gu, A. C. Jasti, M. Jansen, and J. E. Siefring RhoH, a hematopoietic-specific Rho GTPase, regulates proliferation, survival, migration, and engraftment of hematopoietic progenitor cells Blood, February 15, 2005; 105(4): 1467 - 1475. [Abstract] [Full Text] [PDF]
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T. Kawahara, M. Kohjima, Y. Kuwano, H. Mino, S. Teshima-Kondo, R. Takeya, S. Tsunawaki, A. Wada, H. Sumimoto, and K. Rokutan 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, February 1, 2005; 288(2): C450 - C457. [Abstract] [Full Text] [PDF]
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A. Yamauchi, C. C. Marchal, J. Molitoris, N. Pech, U. Knaus, J. Towe, S. J. Atkinson, and M. C. Dinauer 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., January 14, 2005; 280(2): 953 - 964. [Abstract] [Full Text] [PDF]
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 M. C. Dinauer Chronic Granulomatous Disease and Other Disorders of Phagocyte Function Hematology, January 1, 2005; 2005(1): 89 - 95. [Abstract] [Full Text] [PDF]
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R. He, M. Nanamori, H. Sang, H. Yin, M. C. Dinauer, and R. D. Ye Reconstitution of Chemotactic Peptide-Induced Nicotinamide Adenine Dinucleotide Phosphate (Reduced) Oxidase Activation in Transgenic COS-phox Cells J. Immunol., December 15, 2004; 173(12): 7462 - 7470. [Abstract] [Full Text] [PDF]
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A. Yamauchi, C. Kim, S. Li, C. C. Marchal, J. Towe, S. J. Atkinson, and M. C. Dinauer Rac2-Deficient Murine Macrophages Have Selective Defects in Superoxide Production and Phagocytosis of Opsonized Particles J. Immunol., November 15, 2004; 173(10): 5971 - 5979. [Abstract] [Full Text] [PDF]
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Y. Kotone-Miyahara, K. Yamashita, K.-K. Lee, S. Yonehara, T. Uchiyama, M. Sasada, and A. Takahashi Short-term delay of Fas-stimulated apoptosis by GM-CSF as a result of temporary suppression of FADD recruitment in neutrophils: evidence implicating phosphatidylinositol 3-kinase and MEK1-ERK1/2 pathways downstream of classical protein kinase C J. Leukoc. Biol., November 1, 2004; 76(5): 1047 - 1056. [Abstract] [Full Text] [PDF]
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M. T. Quinn and K. A. Gauss Structure and regulation of the neutrophil respiratory burst oxidase: comparison with nonphagocyte oxidases J. Leukoc. Biol., October 1, 2004; 76(4): 760 - 781. [Abstract] [Full Text] [PDF]
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K. Nigorikawa, N. Okamura, and O. Hazeki The Effect of Anionic Amphiphiles on the Recruitment of Rac in Neutrophils J. Biochem., October 1, 2004; 136(4): 463 - 470. [Abstract] [Full Text] [PDF]
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D. Abdel-Latif, M. Steward, D. L. Macdonald, G. A. Francis, M. C. Dinauer, and P. Lacy Rac2 is critical for neutrophil primary granule exocytosis Blood, August 1, 2004; 104(3): 832 - 839. [Abstract] [Full Text] [PDF]
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B. A. Diebold, B. Fowler, J. Lu, M. C. Dinauer, and G. M. Bokoch Antagonistic Cross-talk between Rac and Cdc42 GTPases Regulates Generation of Reactive Oxygen Species J. Biol. Chem., July 2, 2004; 279(27): 28136 - 28142. [Abstract] [Full Text] [PDF]
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J.-S. Kim, B. A. Diebold, J.-I. Kim, J. Kim, J.-Y. Lee, and J.-B. Park Rho Is Involved in Superoxide Formation during Phagocytosis of Opsonized Zymosans J. Biol. Chem., May 14, 2004; 279(20): 21589 - 21597. [Abstract] [Full Text] [PDF]
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 E. Werner GTPases and reactive oxygen species: switches for killing and signaling J. Cell Sci., January 15, 2004; 117(2): 143 - 153. [Abstract] [Full Text] [PDF]
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D. Pradip, X. Peng, and D. L. Durden Rac2 Specificity in Macrophage Integrin Signaling: POTENTIAL ROLE FOR Syk KINASE J. Biol. Chem., October 24, 2003; 278(43): 41661 - 41669. [Abstract] [Full Text] [PDF]
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C. Kim, C. C. Marchal, J. Penninger, and M. C. Dinauer The Hemopoietic Rho/Rac Guanine Nucleotide Exchange Factor Vav1 Regulates N-Formyl-Methionyl-Leucyl-Phenylalanine-Activated Neutrophil Functions J. Immunol., October 15, 2003; 171(8): 4425 - 4430. [Abstract] [Full Text] [PDF]
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M. Glogauer, C. C. Marchal, F. Zhu, A. Worku, B. E. Clausen, I. Foerster, P. Marks, G. P. Downey, M. Dinauer, and D. J. Kwiatkowski Rac1 Deletion in Mouse Neutrophils Has Selective Effects on Neutrophil Functions J. Immunol., June 1, 2003; 170(11): 5652 - 5657. [Abstract] [Full Text] [PDF]
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A. Dumortier, P. Kirstetter, P. Kastner, and S. Chan Ikaros regulates neutrophil differentiation Blood, March 15, 2003; 101(6): 2219 - 2226. [Abstract] [Full Text] [PDF]
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G. M. Fuhler, A. L. Drayer, and E. Vellenga Decreased phosphorylation of protein kinase B and extracellular signal-regulated kinase in neutrophils from patients with myelodysplasia Blood, February 1, 2003; 101(3): 1172 - 1180. [Abstract] [Full Text] [PDF]
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J. A. Carlyon, W.-T. Chan, J. Galan, D. Roos, and E. Fikrig Repression of rac2 mRNA Expression by Anaplasma phagocytophila Is Essential to the Inhibition of Superoxide Production and Bacterial Proliferation J. Immunol., December 15, 2002; 169(12): 7009 - 7018. [Abstract] [Full Text] [PDF]
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Y. Gu, M. C. Byrne, N. C. Paranavitana, B. Aronow, J. E. Siefring, M. D'Souza, H. F. Horton, L. A. Quilliam, and D. A. Williams Rac2, a Hematopoiesis-Specific Rho GTPase, Specifically Regulates Mast Cell Protease Gene Expression in Bone Marrow-Derived Mast Cells Mol. Cell. Biol., November 1, 2002; 22(21): 7645 - 7657. [Abstract] [Full Text] [PDF]
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S. Li, A. Yamauchi, C. C. Marchal, J. K. Molitoris, L. A. Quilliam, and M. C. Dinauer 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., November 1, 2002; 169(9): 5043 - 5051. [Abstract] [Full Text] [PDF]
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M. O. Price, S. J. Atkinson, U. G. Knaus, and M. C. Dinauer Rac Activation Induces NADPH Oxidase Activity in Transgenic COSphox Cells, and the Level of Superoxide Production Is Exchange Factor-dependent J. Biol. Chem., May 17, 2002; 277(21): 19220 - 19228. [Abstract] [Full Text] [PDF]
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M. O. Price, L. C. McPhail, J. D. Lambeth, C.-H. Han, U. G. Knaus, and M. C. Dinauer Creation of a genetic system for analysis of the phagocyte respiratory burst: high-level reconstitution of the NADPH oxidase in a nonhematopoietic system Blood, April 15, 2002; 99(8): 2653 - 2661. [Abstract] [Full Text] [PDF]
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T. Adachi, R. Vita, S. Sannohe, S. Stafford, R. Alam, H. Kayaba, and J. Chihara The Functional Role of Rho and Rho-Associated Coiled-Coil Forming Protein Kinase in Eotaxin Signaling of Eosinophils J. Immunol., October 15, 2001; 167(8): 4609 - 4615. [Abstract] [Full Text] [PDF]
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| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
