Search results for "Adhesion"
showing 10 items of 1165 documents
Diverse cell surface protein ectodomains are shed by a system sensitive to metalloprotease inhibitors.
1996
The extracellular domains of a diverse group of membrane proteins are shed in response to protein kinase C activators such as phorbol 12-myristate 13-acetate (PMA). The lack of sequence similarity in the cleavage sites suggests the involvement of many proteases of diverse specificity in this process. However, a mutant Chinese hamster ovary cell line recently isolated for being defective in PMA-activated shedding of the membrane-anchored growth factor transforming growth factor alpha precursor (proTGF-alpha) is concomitantly defective in the shedding of many other unrelated membrane proteins. Here we show that independent mutagenesis and selection experiments yield shedding mutants having th…
Morpholino knockdown of the ubiquitously expressed transmembrane serine protease TMPRSS4a in zebrafish embryos exhibits severe defects in organogenes…
2011
AbstractOver the past years the members of the type II transmembrane serine protease (TTSP) family have emerged as new players in mammalian biology. TMPRSS4 (transmembraneprotease/serine) is overexpressed in several human cancer tissues, promoting invasion, migration, and metastasis. However, the physiological function has not yet been elucidated. Here, we present morpholino knockdown studies targeting TMPRSS4a, a homolog of human TMPRSS4 in zebrafish embryos. By RT-PCR, we could demonstrate an expression of this protease already 5 h post-fertilization, suggesting important functions in the early stages of embryonic development. Indeed,in vivogene silencing caused severe defects in tissue d…
Kinetics of thrombomodulin release and endothelial cell injury by neutrophil-derived proteases and oxygen radicals
2002
Thrombomodulin is a transmembranous glycoprotein of endothelial cells. In vitro it is a marker of endothelial cell injury. In vivo the levels of serum thrombomodulin are regarded as a parameter of activity in vasculitides. The latter are pathophysiologically determined by neutrophil-derived inflammation and endothelial cell injury caused by secretion of proteases and hydrogen peroxide. It was the objective of this study to determine whether thrombomodulin is only a late marker of advanced endothelial cell injury or whether it indicates also earlier stages of cell alterations. Over 24 hr endothelial cell cultures were incubated with hydrogen peroxide or the neutrophil proteases proteinase-3,…
Specific processing of tenascin-C by the metalloprotease meprinβ neutralizes its inhibition of cell spreading
2009
The metalloprotease meprin has been implicated in tissue remodelling due to its capability to degrade extracellular matrix components. Here, we investigated the susceptibility of tenascin-C to cleavage by meprinbeta and the functional properties of its proteolytic fragments. A set of monoclonal antibodies against chicken and human tenascin-C allowed the mapping of proteolytic fragments generated by meprinbeta. In chicken tenascin-C, meprinbeta processed all three major splicing variants by removal of 10kDa N-terminal and 38kDa C-terminal peptides, leaving a large central part of subunits intact. A similar cleavage pattern was found for large human tenascin-C variant where two N-terminal pep…
Integrative genomic and proteomic analyses identify targets for Lkb1 deficient metastatic lung tumors
2010
SummaryIn mice, Lkb1 deletion and activation of KrasG12D results in lung tumors with a high penetrance of lymph node and distant metastases. We analyzed these primary and metastatic de novo lung cancers with integrated genomic and proteomic profiles, and have identified gene and phosphoprotein signatures associated with Lkb1 loss and progression to invasive and metastatic lung tumors. These studies revealed that SRC is activated in Lkb1-deficient primary and metastatic lung tumors, and that the combined inhibition of SRC, PI3K, and MEK1/2 resulted in synergistic tumor regression. These studies demonstrate that integrated genomic and proteomic analyses can be used to identify signaling pathw…
C7 is expressed on endothelial cells as a trap for the assembling terminal complement complex and may exert anti-inflammatory function.
2009
AbstractWe describe a novel localization of C7 as a membrane-bound molecule on endothelial cells (ECs). Data obtained by sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS-PAGE), Western blot analysis, Northern blot analysis, and mass spectrometry revealed that membrane-associated C7 (mC7) was indistinguishable from soluble C7 and was associated with vimentin on the cell surface. mC7 interacted with the other late complement components to form membrane-bound TCC (mTCC). Unlike the soluble SC5b-9, mTCC failed to stimulate ECs to express adhesion molecules, to secrete IL-8, and to induce albumin leakage through a monolayer of ECs, and more importantly protected ECs from the proinf…
Exploration of the Sea Urchin Coelomic Fluid via Combinatorial Peptide Ligand Libraries
2012
The urchin Paracentrotus lividus has been characterized via previous capture and enhancement of low-abundance proteins with combinatorial peptide ligand libraries (CPLL, ProteoMiner). Whereas in the control only 26 unique gene products could be identified, 82 species could be detected after CPLL treatment. Due to the overwhelming presence of two major proteins-the toposome (a highly glycosylated, modified calcium-binding, iron-less transferrin) and the major yolk proteins, belonging to the class of cell adhesion proteins-which constituted about 70% of the proteome of this biological fluid and strongly interfered with the capture of the minority proteome, no additional proteins could be dete…
Establishment and comparative characterization of novel squamous cell non-small cell lung cancer cell lines and their corresponding tumor tissue.
2010
Abstract Background Cell lines play an important role for studying tumor biology and novel therapeutic agents. Particularly in pulmonary squamous cell carcinoma (SCC) the availability of cell lines is limited and knowledge about their representativeness for corresponding tumor tissue is scanty. Materials and methods We established three novel SCC cell lines from fresh tumor tissue of 28 donors, including 8 SCC. Two cell lines were derived from different localizations of the same donor, i.e. primary tumor and lymph node metastasis. This represents a so far unique combination in lung cancer. The genotypes, gene expression profiles and mutational status of epidermal growth factor receptor ( EG…
Chronic obstructive pulmonary disease and neutrophil infiltration: role of cigarette smoke and cyclooxygenase products.
2010
Cigarette smoke is the main cause of chronic obstructive pulmonary disease (COPD), where it can contribute to the observed airway inflammation. PGE(2) is produced within human airways, and both pro- and anti-inflammatory activities have been reported. We quantitated PGE(2) concentrations in induced sputum supernatants from different groups of subjects and correlated the obtained values to neutrophil infiltration as well as to the expression of cyclooxygenase-2 (COX-2). Cigarette smoke extract (CSE) was used to evaluate the effect of smoking on COX-2 and PGE(2) receptor expression as well as on PGE(2) release in neutrophils and alveolar macrophages (AM) obtained from normal donors. The effec…
Oral N-acetylcysteine attenuates the rat pulmonary inflammatory response to antigen.
2003
Oxidative stress is involved in the pathophysiology of inflammatory airway diseases including asthma; therefore, antioxidants might be of clinical benefit in asthma treatment. In the present study, the effects of N-acetylcysteine on sensitised brown Norway rats were examined. N-Acetylcysteine (3 mmol kg body weight(-1) administered orally) was given daily for 1 week before challenge and various antigen-induced pulmonary responses were studied. Antigen exposure increased lipid peroxidation in bronchoalveolar lavage fluid (BALF) and oxidised glutathione levels in lung tissue 2 h after challenge. Lung nuclear transcription factor-KB-binding activity was increased 2 h after challenge, and BALF …