Tissue plasminogen activating factor

Plasmin is responsible for the breakdown of fibrin and is formed from plasminogen via the action of tissue plasminogen activating factor (TPA) which is a serine protease. TPA forms plasmin by deaving plasminogen at the C-terminus side of a lysine residue. In common with all... 

For biotechnologically produced mammalian proteins such as erythropoietin and tissue plasminogen activating factor the correct glycosylation pattern is essential for activity. 

Protein G. This vitamin K-dependent glycoproteia serine protease zymogen is produced ia the Hver. It is an anticoagulant with species specificity (19—21). Proteia C is activated to Proteia by thrombomodulin, a proteia that resides on the surface of endothefial cells, plus thrombin ia the presence of calcium. In its active form, Proteia selectively iaactivates, by proteolytic degradation. Factors V, Va, VIII, and Villa. In this reaction the efficiency of Proteia is enhanced by complex formation with free Proteia S. la additioa, Proteia activates tissue plasminogen activator, which... 

Tissue plasminogen activators Human growth hormone Neuroactive peptides Regulatory peptides Lymphokines Human serum albumin Gamma globulin Antihemophilic factors Monoclonal antibodies... 

Larrue V, von Kummer RR, Muller A, Bluhmki E. Risk factors for severe hemorrhagic transformation in ischemic stroke patients treated with recombinant tissue plasminogen activator A secondary analysis of the european-australasian acute stroke study (ECASS II). Stroke. 2001 32 438 1. 

The antithrombotic factors produced by endothelial cells are thrombomodulin (TM) and protein S (PS), components of the vitamin K-dependent protein C (PC) anticoagulant pathway, inhibiting F-Va-F-Villa (E15) tissue plasminogen activator (tPA), responsible for fibrinolysis (N2, LI8) and the lipoprotein-associated coagulation inhibitor (LACI), which inhibits F-VIIa-TF complex and F-Xa (B51). 

Mammalian cell suspension cultures are the preferred choice for large-scale recombinant protein production in stirred-tank bioreactors. The most widely used systems are Chinese hamster ovary (CHO) cells and the murine myeloma fines NSO and SP2/0. In half of the biological license approvals from 1996-2000, CHO cells were used for the production of monoclonal antibodies and other recombinant glycosylated proteins, including tPA (tissue plasminogen activator) and an IgGl fusion with the tumor necrosis factor (TNF) receptor, the latter marketed as Enbrel [7]. 

Sundell, I. B., Nilsson, T. K., Hallmans, G., Hellsten, G., and Dahlen, G. H., Interrelationships between plasma levels of plasminogen activator inhibitor, tissue plasminogen activator, lipoprotein (a) and established cardiovascular risk factors in a North Swedish population. Atherosclerosis (Shannon, Irel.) 80, 9-16 (1989). 

Fig. 7. The arrangement of domains along human tissue plasminogen activator (SWISS-PROT UROT HUMAN, top of the figure) and human Factor XII (SWISS-PROT FA12 HUMAN, bottom of the figure). FNI and FNII are fibronectin class I and II domains, respectively.

Along with the production of insulin, many other medical uses have been achieved for recombinant DNA. This includes the production of erythropoetin, a hormone used to stimulate production of red blood cells in anemic people tissue plasminogen activator, an enzyme that dissolves blood clots in heart attack victims and antihemophilic human factor VIII, used to prevent and control bleeding for hemophiliacs. These three important genetically engineered proteins were all cloned in hamster cell cultures. 

Tissue plasminogen activator Tumour necrosis factor Monoclonal antibody preparations y-Globulin preparations Hepatitis B surface antigen... 

AC VIII, adenylyl cyclase type VIII BDNF, brain-derived neurotrophic factor CamKII, calcium-calmodulin kinase II GIRK2, G protein-activated inward rectifying potassium 2 MAOA, monoamine oxidase A n.d., not determined NCAM, neural cell adhesion molecule nNOS, neuronal nitric oxide synthase Petl, ETS domain transcription factor tPA, serine protease tissue-plasminogen activator (tPA). t/ > Increase/decrease in anxiety-related behavior. No effect. 

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