Urokinase-type plasminogen activator protein

In a different approach, a TNF fusion protein designated TNF-Selectokine has been described [5]. This TNF prodrug is comprised of a trimeric scFv-TNF fusion protein to which a TNFR fragment has been fused at the C-terminal. A flexible peptide linker between TNF and the blocking receptor domain is comprised of sequences specifically recognized by tumor associated proteases such as tissue plasminogen activator, urokinase type plasminogen activator or... 

Urokinase-type plasminogen activator (uPA, urokinase) is synthesized by endothelial and tumor cells as a single-chain glycoprotein (scuPA) without catalytic activity. When it is converted to a two-chain protein (tcuPA) by plasmin, an active serine protease center develops, which activates plasminogen. Thus, uPA (55 kDa) results in the amplification of fibrinolysis. 

D10. Dumler, I. T., Petri, T., and Schleuning, W. D., Interaction of urokinase-type plasminogen activator (uPA) with its cellular receptor (uPAR) induces phosphorylation on tyrosine of a 38 kDa protein. FEBS Lett. 322, 37-40 (1993). 

Kofoed, K., et al. (2007) Use of plasma C-reactive protein, procalcitonin, neutrophils, macrophage migration inhibitory factor, soluble urokinase-type plasminogen activator receptor, and soluble triggering receptor expressed on myeloid cells-1 in combination to diagnose infections a prospective study. Crit Care. 11, R38. 

Nielsen LS, Kellerman GM, Behrendt N, Picone R, Dano K, Blasi F. A 55,000-60,000 Mr receptor protein for urokinase-type plasminogen activator. Identification in human tumor cell lines and partial purification. J Biol Chem 1988 263(5) 2358—2363. 

Ploug M, Kjalke M, Ronne E, Weidle U, Hoyer-Hansen G, Dano K. Localization of the disulfide bonds in the NH2-terminal domain of the cellular receptor for human urokinase-type plasminogen activator. A domain structure belonging to a novel superfamily of glycolipid-anchored membrane proteins. J Biol Chem 1993 268(23) 17539-17546. 

Bi L, Sarkar R, Naas T et aL (1996) Further characterization of Factor VUI-deficient mice created by gene targeting RNA and protein studies. Blood 88 3446-3450 Bugge TH, Suh TT, Flick MJ et al. (1995) The receptor for urokinase-type plasminogen activator is not essential for mouse development or fertility. J Bio Chem 270 16886-16894... 

Ol. Odet, F., Guyot, R., Leduque, P., and Le Margueresse-Battistoni, B., Evidence for similar expression of protein C inhibitor and the urokinase-type plasminogen activator system during mouse testis development. Endocrinology 145, 1481-1489 (2004). 

MDM = SLURP Mai de Meleda palmoplantar keratosis due to mutation in chromosome 8q24-qter in gene of secreted lymphocyte antigen-6 urokinase-type plasminogen-activator receptor-related protein, that is not to be mistaken for MDM as above. Click for SLURP by Eckl KM et al and/or Wajid M et al. 

Urokinase-type plasminogen activator (EC 3.4.21.73) is synthesised in a single-chain form and is converted to an active, two chain form after it binds to its cell surface receptor, uPAR. Treatment human of alveolar type II cells (A549) with 1 to 5 jUM chromium(Vl) for 4 and 12 h decreased both the specific activity and the amount of uPA protein (Shumilla and Barchowsky 1999). Chromium reduced uPA protein levels by inhibiting protein synthesis and had no effect on uPA mRNA levels or the rate of uPA protein degradation. In contrast, both mRNA and protein levels for the uPA receptor were increased by treatment with concentrations of chromium(VI) that did not completely inhibit protein synthesis. 

In addition to binding lipoproteins, the LRP also binds to a2-macroglobulin, a plasma protein that binds to proteases and, upon binding, is cleared by the liver. The LRP also binds to plasminogen activators and their inhibitors, such as tissue-type plasminogen activator, urokinase-type plasminogen activator, and their corresponding inhibitors. 

Tincture of the dried seed, on agar plate at a concentration of 30 p,L/disc, was inactive on Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. Extract of 10 g plant material in 100 mL ethanol was used b Anticoagulation activity. Serpin BSZx (an inhibitor of trypsin and chemotrypsin) inhibited thrombin, plasma kallikrein, factor Vlla/tissue factor, and factor Xa at heparin-independent association rates. Only factor Xa turned a significant fraction of BSZx over as substrate. Activated protein C and leukocyte elastase were slowly inhibited by BSZx, whereas factor Xlla, urokinase and tissue type plasminogen activator, plasmin and pancreas kallikrein, and elastase were not or only weakly affected. Trypsin from Fusarium was not inhibited, while interaction with subtilisin Carlsberg and Novo was rapid, but most BSZx was cleaved as a substrate L... 

D3. De Petro, G., Tavian, D., Mrchina, E., and Barlati, S., Induction of fibronectin mRNA by urokinase- and tissue-type plasminogen activator in human skin fibroblasts Differential role of u-PA and t-PA at the fibronectin protein level. Biol. Chem. 383, 177-187 (2002). 

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