A5024130203- Protease and Inhibitor Mechanisms
- Cell Adhesion Molecules Research
- Cytomegalovirus and herpesvirus research
- Metalloenzymes and iron-sulfur proteins
- Blood Coagulation and Thrombosis Mechanisms
- Monoclonal and Polyclonal Antibodies Research
- RNA modifications and cancer
- Peptidase Inhibition and Analysis
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Herpesvirus Infections and Treatments
- Osteoarthritis Treatment and Mechanisms
- Glycosylation and Glycoproteins Research
- HER2/EGFR in Cancer Research
- Muscle metabolism and nutrition
- Protein Kinase Regulation and GTPase Signaling
- Galectins and Cancer Biology
- Synthesis and Characterization of Heterocyclic Compounds
- Nutritional Studies and Diet
- Immune Response and Inflammation
- Renal Diseases and Glomerulopathies
- Endoplasmic Reticulum Stress and Disease
- Cytokine Signaling Pathways and Interactions
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Metabolism and Genetic Disorders
- Blood properties and coagulation
Confluence Life Sciences (United States)
2019-2024
Pfizer (United States)
2004-2020
Collegium Helveticum
2006
ETH Zurich
2006
National Eye Institute
1996
National Institutes of Health
1983-1996
Monsanto (United States)
1986-1996
University of California, San Diego
1995
Amgen (United States)
1995
Weatherford College
1994
SphK (sphingosine kinase) is the major source of bioactive lipid and GPCR (G-protein-coupled receptor) agonist S1P 1-phosphate). promotes cell growth, survival migration, a key regulator lymphocyte trafficking. Inhibition signalling has been proposed as strategy for treatment inflammatory diseases cancer. In present paper we describe discovery characterization PF-543, novel cell-permeant inhibitor SphK1. PF-543 inhibits SphK1 with K(i) 3.6 nM, sphingosine-competitive more than 100-fold...
Autotaxin is the enzyme responsible for production of lysophosphatidic acid (LPA) from lysophosphatidyl choline (LPC), and it up-regulated in many inflammatory conditions, including but not limited to cancer, arthritis, multiple sclerosis. LPA signaling causes angiogenesis, mitosis, cell proliferation, cytokine secretion. Inhibition autotaxin may have anti-inflammatory properties a variety diseases; however, this hypothesis has been tested pharmacologically because lack potent inhibitors....
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCell-type-specific and site-specific N-glycosylation of type I II human tissue plasminogen activatorRaj B. Parekh, Raymond A. Dwek, Jerry R. Thomas, Ghislain Opdenakker, Thomas W. Rademacher, Arthur J. Wittwer, Susan C. Howard, Rickey Nelson, Ned Siegel, M Jennings, Nikos Harakas, Joseph FederCite this: Biochemistry 1989, 28, 19, 7644–7662Publication Date (Print):September 1989Publication History Published online1 May 2002Published inissue 19...
Osteoarthritis is characterized by the loss of aggrecan and collagen from cartilage extracellular matrix. The proteinases responsible for breakdown include ADAMTS-4 (aggrecanase 1) ADAMTS-5 2). Post-translational inhibition ADAMTS-4/-5 activity may be important maintaining normal homeostasis metabolism, thus, any disruption to this could lead accelerated breakdown. To date TIMP-3 (tissue inhibitor matrix metalloproteinases-3) only endogenous that has been identified. In present studies we...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEffects of N-glycosylation on in vitro activity Bowes melanoma and human colon fibroblast-derived tissue plasminogen activatorArthur J. Wittwer, Susan C. Howard, Linda S. Carr, Nikos K. Harakas, Joseph Feder, Raj B. Parekh, Pauline M. Rudd, Raymond A. Dwek, Thomas W. RademacherCite this: Biochemistry 1989, 28, 19, 7662–7669Publication Date (Print):September 1989Publication History Published online1 May 2002Published inissue 19 September...
Escherichia coli, Clostridium sticklandii, and Methanococcus vannielii synthesize 75Se-labeled amino acid transfer ribonucleic acids [( 75Se]tRNAs) when grown with low levels (approximately equal to 1 microM) of 75SeO32-. When E. coli [75Se]tRNA was digested nucleosides analyzed by reversed-phase high-performance liquid chromatography, a single selenonucleoside accounted for 70-90% the 75Se label in bulk tRNA. This nucleoside shown be indistinguishable number its properties from authentic...
to the presence of two folatebinding proteins
The purified folate-binding proteins of rat liver mitochondria have been identified as two separate enzymes: dimethylglycine dehydrogenase (EC 1.5.99.2) and sarcosine (E.C. 1.5.99.1) (Wittwer,
The epidermis is a barrier that prevents water loss while keeping harmful substances from penetrating the host. impermeable cornified layer of stratum corneum maintained by balancing continuous turnover driven epidermal basal cell proliferation, suprabasal differentiation, and corneal shedding. desquamation process tightly regulated balance activities serine proteases Kallikrein-related peptidases (KLK) family their cognate inhibitor lymphoepithelial Kazal type-related (LEKTI), which encoded...
Cytokine-induced neutrophil chemoattractant (CINC), a chemotactic molecule of the interleukin (IL)-8 family, is known to be induced in rat response tumor necrosis factor (TNF), IL-1, and lipopolysaccharide (LPS). Intratracheal injection endotoxin (LPS) shown cause CINC mRNA expression pulmonary tissue, peaking after 2 h, protein bronchoalveolar lavage (BAL) fluid, 2–4 h. synthetic causes acute inflammation that abrogated by coinjection antiserum purified natural CINC. inhibits intratracheal...
Chemokines are a family of cytokines whose participation in inflammation vivo remains to be established. Using the rat model anti-glomerular basement membrane (GBM) nephritis, we found that mRNA for chemokine CINC (cytokine-induced neutrophil chemoattractant) was induced kidney, and corresponding protein elaborated by isolated inflamed glomeruli. Production glomeruli unaffected complement- or leukocyte-depletion prior disease induction. Cytokines which induce expression renal cells...
Several inhibitors of a series cis-1(S)2(R)-amino-2-indanol-based compounds were reported to be selective for the aggrecanases, ADAMTS-4 and -5 over other metalloproteases. To understand nature this selectivity inhibitors, along with broad spectrum metalloprotease inhibitor marimastat, independently bound catalytic domain ADAMTS-5, corresponding crystal structures determined. By comparing structures, it was determined that specificity relative ADAMTS-5 not driven by specific interaction,...
Tissue-type plasminogen activator (tPA) is a glycosylated serine protease which an effective thrombolytic agent. Native single-chain tPA (sc-tPA) converted to two-chain (tc-tPA) by plasmin, the product of reaction with tPA. sc-tPA occurs as two glycoforms. Type I fully glycosylated, while type II lacks glycosylation at Asn-184. The rates and human melanoma were tc-tPA plasmin determined different methods. In each case, second-order rate constant (kcat/Km) for (approximately 8 microM-1 s-1)...
Amino acid transfer nucleic acids (tRNAs) that contain selenium-modified bases are synthesized by Escherichia coli in the presence of low levels (0.1-0.5 microM) [75Se]selenite or [75Se]selenate. The amount selenium incorporated (1-2 g atoms/100 mol tRNA) was unchanged 10-20-fold variations sulfate concentrations addition 1 mM cysteine, sulfide, sulfite. Specific incorporation (as opposed to nonspecific substitution for sulfur) further indicated different reversed phase chromatographic...
The folate-binding protein of rat liver mitochondria [Zamierowski, M. & Wagner, C. (1977) J. Biol. Chem. 252, 933-938] has been purified to homogeneity by a combination gel filtration, DEAE-cellulose, and affinity chromatography. This was assayed its ability bind tetrahydro[3H]folic acid in vitro. the contains tightly bound flavin molecular weight about 90,000 as determined sodium dodecyl sulfate electrophoresis. also displays dimethylglycine dehydrogenase [N,N-dimethylglycine:...
The serpin-enzyme complex (SEC) receptor recognizes a pentapeptide neo-domain of alpha 1-antitrypsin (alpha 1 AT)-elastase complexes and, in so doing, mediates internalization and intracellular catabolism the macromolecular complex, an increase synthesis AT, elicits neutrophil chemotactic activity. In previous studies we have shown that this domain is highly conserved among members serpin family binding synthetic peptide corresponding to region (125I-peptide 105Y, SIP-PEVKFNKPFVYLI, based on...
Chemokines may be important in the pathogenesis of glomerular leukocyte infiltration antiglomerular basement membrane (GBM) antibody (Ab) glomerulonephritis (GN). We studied expression C-C chemokines [macrophage inflammatory protein (MIP)-1 alpha, monocyte chemotactic (MCP)-1, and RANTES] C-X-C [platelet factor 4 (PF4), interferon-inducible 10 kDa (IP-10), MIP-2, cytokine-induced neutrophil chemoattractant (CINC)] at 30 min, 3, 6, 9, 15, 24 h after induction heterologous-phase anti-GBM Ab GN...