scholarly journals Kunitz-type protease inhibitor bikunin disrupts phorbol ester-induced oligomerization of CD44 variant isoforms containing epitope v9 and subsequently suppresses expression of urokinase-type plasminogen activator in human chondrosarcoma cells.

2002 ◽  
Vol 277 (18) ◽  
pp. 16346
Author(s):  
Mika Suzuki ◽  
Hiroshi Kobayashi ◽  
Michio Fujie ◽  
Takashi Nishida ◽  
Masaharu Takigawa ◽  
...  
Keyword(s):  
Protease Inhibitor ◽  
Phorbol Ester ◽  
Cd44 Variant ◽  
Human Chondrosarcoma ◽  
Variant Isoforms ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator ◽  
Kunitz Type ◽  
Kunitz Type Protease Inhibitor ◽  
Cd44 Variant Isoforms

scholarly journals Phorbol ester induces the biosynthesis of glycosylated and nonglycosylated plasminogen activator inhibitor 2 in high excess over urokinase-type plasminogen activator in human U-937 lymphoma cells.

1987 ◽  
Vol 104 (3) ◽  
pp. 705-712 ◽  
Author(s):  
C Genton ◽  
E K Kruithof ◽  
W D Schleuning
Keyword(s):  
Plasminogen Activator ◽  
Phorbol Ester ◽  
Large Scale ◽  
De Novo ◽  
Plasminogen Activator Inhibitor ◽  
Conditioned Media ◽  
Cell Extracts ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator ◽  
Activator Inhibitor

The tumor-promoting phorbol ester PMA induces changes in the histiocytic human lymphoma cell line U-937 akin to cellular differentiation (Ralph, P., N. Williams, M. A. S. Moore, and P. B. Litcofsky, 1982, Cell. Immunol., 71:215-223) and concomitantly stimulates the biosynthesis of plasminogen activator inhibitor 2 (PAI 2) and of urokinase-type plasminogen activator (u-PA). PAI 2 is found in a nonglycosylated intracellular and a glycosylated secreted form. The former appears to be identical to PAI 2 previously purified from placental extracts and large-scale U-937 cell cultures. The sixfold increase of PAI 2 antigen measured 24 h after PMA treatment in cell extracts and conditioned media is accompanied by an equal increase of active PAI 2 mRNA, whereas the 6 to 13-fold increase of u-PA antigen in the same samples is associated with only a 1.5-fold mRNA increase. The increase of PAI 2, but not of u-PA, biosynthesis requires transcription. A 50-fold molar excess of PAI 2 over u-PA is found in both extracts and conditioned media of PMA-treated cells. PAI 2 represents at least 0.3% of total de novo synthesized protein 24 h after induction with PMA. Thus, PAI 2, but not u-PA, is an abundant product of this precursor analogue of the mononuclear phagocyte lineage, and might represent a new marker for monocyte/macrophage differentiation.

Ultra-Rapid Cardiotoxicity of the Hepatitis C Virus Protease Inhibitor BILN 2061 in the Urokinase-Type Plasminogen Activator Mouse

2007 ◽  
Vol 133 (4) ◽  
pp. 1144-1155 ◽  
Author(s):  
Thomas Vanwolleghem ◽  
Philip Meuleman ◽  
Louis Libbrecht ◽  
Tania Roskams ◽  
Rita De Vos ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Protease Inhibitor ◽  
Plasminogen Activator ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator

scholarly journals Enhanced Plasmin Inhibition by a Reactive Center Lysine Mutant of the Kunitz-type Protease Inhibitor Domain of the Amyloid β-Protein Precursor

1995 ◽  
Vol 270 (39) ◽  
pp. 22827-22830 ◽  
Author(s):  
William E. Van Nostrand ◽  
Alvin H. Schmaier ◽  
Robert S. Siegel ◽  
Steven L. Wagner ◽  
William C. Raschke
Keyword(s):  
Protease Inhibitor ◽  
Amyloid Β ◽  
Amyloid Β Protein ◽  
Protein Precursor ◽  
Β Protein ◽  
Reactive Center ◽  
Kunitz Type ◽  
Kunitz Type Protease Inhibitor

scholarly journals Expression and modulation of CD44 variant isoforms in humans

1994 ◽  
Vol 124 (1) ◽  
pp. 71-82 ◽  
Author(s):  
CR Mackay ◽  
HJ Terpe ◽  
R Stauder ◽  
WL Marston ◽  
H Stark ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Metastasis ◽  
Cell Types ◽  
The Body ◽  
Basal Cells ◽  
Ifn Gamma ◽  
Cd44 Variant ◽  
Variant Isoforms ◽  
And Function ◽  
Cd44 Variant Isoforms

CD44 is a ubiquitous surface molecule that exists as a number of isoforms, generated by alternative splicing of 10 "variant" exons. Little is known about the expression and function of the variant isoforms, except that certain isoforms may play a role in cancer metastasis. We produced mAbs against CD44 variant regions encoded by exons 4v, 6v, and 9v, by immunizing mice with a fusion protein spanning variant exons 3v to 10v. A comprehensive analysis of human tissues revealed that CD44 variant isoforms were expressed widely throughout the body, principally by epithelial cells. However there was differential expression of CD44 variant exons by different epithelia. Most epithelia expressed exon 9v, but much fewer expressed 6v or 4v. The regions of epithelia that expressed the highest levels of the variant isoforms were the generative cells, particularly the basal cells of stratified squamous epithelium, and of glandular epithelium. CD44 variant isoforms were also expressed differentially by leukocytes, with CD44-9v expressed at very low levels and CD44-6v and 4v virtually absent. However, CD44-9v and CD44-6v were the main variants that were transiently upregulated on T cells after mitogenic stimulation and on myelomonocytic cell lines by TNF alpha and IFN gamma treatment. Some epithelial cell lines could preferentially upregulate CD44-6v upon IFN gamma incubation. These results show that CD44 variant isoforms are expressed much more widely than first appreciated, and that expression of the variant isoforms on some cell types can be modulated by particular cytokines.

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