A5101587699- Protease and Inhibitor Mechanisms
- Peptidase Inhibition and Analysis
- Blood Coagulation and Thrombosis Mechanisms
- Advanced Proteomics Techniques and Applications
- Cell Adhesion Molecules Research
- Signaling Pathways in Disease
- RNA and protein synthesis mechanisms
- S100 Proteins and Annexins
- Enzyme Production and Characterization
- HIV Research and Treatment
- SARS-CoV-2 and COVID-19 Research
- Obstructive Sleep Apnea Research
- Computational Drug Discovery Methods
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Galectins and Cancer Biology
- Biochemical and Structural Characterization
- Chemokine receptors and signaling
- Advanced Glycation End Products research
- Biological Stains and Phytochemicals
- Airway Management and Intubation Techniques
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Cerebrovascular and genetic disorders
- Influenza Virus Research Studies
- Tannin, Tannase and Anticancer Activities
- Bone and Dental Protein Studies
University of British Columbia
2014-2024
3v Geomatics (Canada)
2023
Walter Reed National Military Medical Center
2017
MRC Laboratory of Molecular Biology
1993-2005
Canadian Institutes of Health Research
2002-2004
University of East Anglia
1998-1999
Queen Mary University of London
1999
Tissue Genetics (United States)
1996
University of Bologna
1990
Rockefeller University
1987
Chemokines provide directional cues for leukocyte migration and activation that are essential normal leukocytic trafficking host responses during processes such as inflammation, infection, cancer. Recently we reported matrix metalloproteinases (MMPs) modulate the activity of CC chemokine monocyte chemoattractant protein-3 by selective proteolysis to release N-terminal tetrapeptide. Here report processing, also at position 4-5, CXC chemokines stromal cell-derived factor (SDF)-1alpha beta...
We have used C-terminal domain mutants to further define the role of interactions progelatinase A and membrane type 1 matrix metalloproteinase (MT1 MMP) in binding TIMP2 cell-associated activation A. Soluble constructs MT1 MMP were demonstrate that with occurs primarily through N-terminal interactions, leaving free for The rate autolytic initiated by cleavage could be potentiated concentration proenzyme heparin. Residues 568–631 are important formation heparin site, since replacement this...
Soluble proenzyme forms of the catalytic domains membrane‐type matrix metalloproteinases 1 and 2 (MT1‐MMP MT2‐MMP) a form MTI‐MMP containing hemopexin were expressed as soluble recombinant proteins. Purified, activated MT‐MMP shown to degrade fibronectin, tenascin, nidogen, aggrecan perlecan. Only MT2‐MMP showed activity against laminin. MT1‐MMP retaining domain was able specifically cleave native type‐I type‐III collagens into 3/4‐1/4 fragments typical specific collagenases. The alone did...
Proteolysis is a major protein posttranslational modification that, by altering structure, affects function and, truncating the sequence, alters peptide signatures of proteins analyzed proteomics. To identify such modified and shortened protease-generated neo-N-termini on proteome-wide basis, we developed whole isobaric tag for relative absolute quantitation (iTRAQ) labeling method that simultaneously labels blocks all primary amines including N- termini lysine side chains. Blocking lysines...
Secreted and membrane tethered matrix metalloproteinases (MMPs) are key homeostatic proteases regulating the extracellular signaling structural environment of cells tissues. For drug targeting proteases, selectivity for individual molecules is highly desired can be met by high yield active site specificity profiling. Using throughput Proteomic Identification protease Cleavage Sites (PICS) method to simultaneously profile both prime non-prime sides cleavage sites nine human MMPs, we...
The role of mast cells and mast-cell-derived factors in natural cytotoxic reactions was investigated. Cultured freshly isolated murine are shown to be WEHI-164 YAC-1 targets 18-hr viability assays but not 4-hr assays. Here, we describe a factor that is immunologically related tumor necrosis (TNF). This TNF-like lyses with slow time course requiring 16-20 hr for the lytic reaction complete. Antibodies specific human TNF lymphotoxin partially block cell lysis cells. These antibodies react on...
Matrix metalloproteinases (MMPs) exert both pro- and antiangiogenic functions by the release of cytokines or proteolytically generated angiogenic inhibitors from extracellular matrix basement membrane remodeling. In Mmp2−/− mouse neovascularization is greatly reduced, but mechanistic aspects this remain unclear. Using isotope-coded affinity tag labeling proteins analyzed multidimensional liquid chromatography tandem mass spectrometry we explored proteome differences between cells those...
Broad-spectrum matrix metalloproteinase (MMP) inhibitors (MMPI) were unsuccessful in cancer clinical trials, partly due to side effects resulting from limited knowledge of the full repertoire MMP substrates, termed substrate degradome, and hence vivo functions MMPs. To gain further insight into degradome MMP-14 (membrane type 1 MMP) an MMPI, prinomastat (drug code AG3340), was used reduce proteolytic processing ectodomain shedding human MDA-MB-231 breast cells transfected with MMP-14. We...
Resolution of inflammation reduces pathological tissue destruction and restores homeostasis. Here, we used a proteomic protease substrate discovery approach, terminal amine isotopic labeling substrates (TAILS), to analyze the role macrophage-specific matrix metalloproteinase-12 (MMP12) in inflammation. In murine peritonitis, MMP12 inactivates antithrombin activates prothrombin, prolonging activated partial thromboplastin time. Furthermore, complement C3 reduce activation chemoattractant...
The main viral protease (3CL
The role of membrane-type (MT) 2-matrix metalloproteinase (MMP) in the cellular activation MMP-2 and tissue inhibitor matrix (TIMP) requirements for this process have not been clearly established. To address these issues a TIMP-2-free cell line derived from <i>Timp2</i>−/− mouse was transfected stable surface expression hMT2-MMP. Untransfected cells did activate endogenous or exogenous unless both TIMP-2 concanavalin A (ConA) were added. Transfected expressing hMT2-MMP efficiently activated...
Membrane-type-1 matrix metalloproteinase has been identified as an activator of the progelatinase A at cell surfaces. We report here that a soluble active form membrane-type-2 can also process in comparable fashion to type-1 rates which are dependent on concentration proenzyme. Activation is inhibited by tissue inhibitors metalloproteinases TIMP-2 and TIMP-3, but only partially TIMP-1. These results suggest cellular activation may be initiated different members membrane-type family depending...
Matrix metalloproteinase-2 (MMP-2, gelatinase A) and membrane type (MT)1-MMP (MMP-14) are cooperative dynamic components of a cell surface proteolytic axis involved in regulating the cellular signaling environment pericellular collagen homeostasis. Although MT1-MMP exhibits I collagenolytic but poor gelatinolytic activities, MMP-2 is potent with weak behavior. Recombinant linker/hemopexin C domain (LCD) binds native collagen, blocks activity trans, by circular dichroism spectroscopy, induces...