A5071718533- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Nitric Oxide and Endothelin Effects
- Immune Response and Inflammation
- Protein Kinase Regulation and GTPase Signaling
- Immune cells in cancer
- Neuroinflammation and Neurodegeneration Mechanisms
- Cell Adhesion Molecules Research
- Adenosine and Purinergic Signaling
- S100 Proteins and Annexins
- Cellular transport and secretion
- Cellular Mechanics and Interactions
- Eicosanoids and Hypertension Pharmacology
- Cardiomyopathy and Myosin Studies
- Redox biology and oxidative stress
- Receptor Mechanisms and Signaling
- Cancer, Hypoxia, and Metabolism
- Hippo pathway signaling and YAP/TAZ
- Congenital heart defects research
- Enzyme Structure and Function
- Phagocytosis and Immune Regulation
- Advanced Glycation End Products research
- Neonatal Health and Biochemistry
- Ubiquitin and proteasome pathways
- Blood disorders and treatments
- Asthma and respiratory diseases
Kyushu University
2016-2025
The University of Tokyo
2009-2014
Osaka International University
2014
Osaka University
2014
Hokkaido University
2009
Japan Science and Technology Agency
2004-2008
Hitachi (Japan)
2005
Science and Technology Corporation (United States)
2004
Centre de Recherche en Économie et Statistique
2004
Centre for Research in Engineering Surface Technology
2004
During phagocytosis, gp91 <sup>phox</sup> , the catalytic subunit of phagocyte NADPH oxidase, becomes activated to produce superoxide, a precursor microbicidal oxidants. Currently increasing evidence suggests that nonphagocytic cells contain similar superoxide-producing oxidases, which are proposed play crucial roles in various events such as cell proliferation and oxygen sensing for erythropoiesis. Here we describe cloning human cDNA encodes novel NAD(P)H designated NOX4. The NOX4 protein...
The catalytic core of a superoxide-producing NADPH oxidase (Nox) in phagocytes is gp91phox/Nox2, membrane-integrated protein that forms heterodimer with p22phox to constitute flavocytochrome b558. cytochrome becomes activated by interacting the adaptor proteins p47phox and p67phox as well small GTPase Rac. Here we describe cloning human cDNAs for novel homologous p67phox, designated p41nox p51nox, respectively; former encoded NOXO1 (Nox organizer 1), latter NOXA1 activator 1). homologue...
The superoxide‐producing NAD(P)H oxidase Nox4 was initially identified as an enzyme that is highly expressed in the kidney and possibly involved oxygen sensing cellular senescence. Although also abundant vascular endothelial cells, its role remains to be elucidated. Here we show preferentially localizes nucleus of human umbilical vein cells (HUVECs), by immunocytochemistry immunoelectron microscopy using three kinds affinity‐purified antibodies raised against distinct immunogens from Nox4....
The superoxide-producing phagocyte NADPH oxidase can be activated by arachidonic acid (AA) or phosphorylation of p47 <sup>phox</sup> under cell-free conditions. molecular mechanism underlying the activation, however, has remained largely unknown. Here we demonstrate that AA, at high concentrations (50–100 μm), induces direct interaction between factors and p22 in parallel with superoxide production. interaction, being required for is mediated via Src homology 3 (SH3) domains...
The small GTPase Rac functions as a molecular switch in several important cellular events including cytoskeletal reorganization and activation of the phagocyte NADPH oxidase, latter which leads to production superoxide, precursor microbicidal oxidants. During formation active oxidase complex at membrane, GTP-bound appears interact with N-terminal region p67(phox), another indispensable activator that translocates from cytosol upon stimulation. Here we show p67(phox) N terminus lacks CRIB...
Activation of the superoxide-producing phagocyte NADPH oxidase requires interaction between p47 <sup>phox</sup> and p22 <sup>phox</sup>, which is mediated via SH3 domains former protein. This considered to be induced by exposure that are normally masked an intramolecular with C-terminal region <sup>phox</sup>. Here we locate SH3-binding site at amino acid residues 286–340, where Ser-303, Ser-304, Ser-328 among several serines known become phosphorylated upon cell stimulation exist....
Protein–phosphoinositide interaction participates in targeting proteins to membranes where they function correctly and is often modulated by phosphorylation of lipids. Here we show that protein p47 phox , a cytoplasmic activator the microbicidal phagocyte oxidase (phox), elicits with phosphoinositides. Although isolated homology (PX) domain can interact directly phosphoinositides, lipid-binding activity this normally suppressed intramolecular PX C-terminal Src 3 (SH3) domain, hence wild-type...
The phagocyte NADPH oxidase is activated during phagocytosis to produce superoxide, a precursor of microbicidal oxidants. activation involves assembly membrane-integrated cytochrome b558 comprising gp91phox and p22phox, two specialized cytosolic proteins (p47phox p67phox), each containing Src homology 3 (SH3) domains, the small G protein Rac. In present study, we show that N-terminal SH3 domain p47phox binds C-terminal cytoplasmic tail p22phox with high affinity (KD = 0.34 µM). binding...
Nox3, a member of the superoxide-producing NADPH oxidase (Nox) family, participates in otoconia formation mouse inner ears, which is required for perception balance and gravity. The activity other Nox enzymes such as gp91(phox)/Nox2 Nox1 known to absolutely require both an organizer protein (p47(phox) or Noxo1) andanactivatorprotein (p67(phox) Noxa1); p47(phox)-dependent activation these oxidases, treatment cells with stimulants phorbol 12-myristate 13-acetate also indispensable. Here we...
Regulated synthesis of reactive oxygen species (ROS) by membrane-bound fungal NADPH oxidases (Nox) plays a key role in morphogenesis, growth, and development. Generation the plant symbiotic fungus, Epichloë festucae , requires functional assembly multisubunit complex composed NoxA, regulatory component, NoxR, small GTPase RacA. However, mechanism for activation this at plasma membrane is unknown. We found yeast two-hybrid coimmunoprecipitation assays that E. NoxR interacts with homologs...
Abstract Reactive oxygen species (ROS) produced by NADPH oxidase 2 (Nox2) function as key mediators of mechanotransduction during both physiological adaptation to mechanical load and maladaptive remodeling the heart. This is despite low levels cardiac Nox2 expression. The mechanism underlying transition from maladaptation remains obscure, however. We demonstrate that transient receptor potential canonical 3 (TRPC3), a Ca 2+ -permeable channel, acts positive regulator ROS (PRROS) in...
The small GTPase Rac participates in various cellular events such as cytoskeletal reorganization. It has remained, however, largely unknown about intracellular signaling pathways for activation because of the lack a simple and reliable assay to estimate activation. Here we describe novel method detect GTP-bound, active cells by pulling it down with Rac-binding domain protein kinase PAK. Experiments using this reveal that stimulation human neutrophils Gi-coupled receptor...
Primary cultures of guinea pig gastric mucosal cells express NADPH oxidase 1 (Nox1), a homolog gp91(phox), and produce superoxide anion (O2-) at rate approximately 100 nmol.mg protein(-1).h(-1) in response to Helicobacter pylori (H. pylori) lipopolysaccharide (LPS) from virulent type I strains. The upregulated O2- production also enhances H. LPS-stimulated tumor necrosis factor-alpha or cyclooxygenase-2 mRNA expression, which suggests potential role for Nox1 the pathogenesis...
Background Asymmetric cell division in the Caenorhabditis elegans embryos requires products of par ( titioning defective) genes 1–6 and atypical protein kinase C (aPKC), whereas Cdc42 Rac, members Rho family GTPases, play an essential role polarity establishment yeast mammalian cells. However, little is known about a link between PAR proteins GTPases polarization. Results Here we have cloned cDNAs for three human homologues PAR6, designated PAR6α, β γ, comprising 345, 372 376 amino acids,...