Tissue plasminogen activator 546836 224254047 2008-07-08T00:37:19Z ProteinBoxBot 3991663 Replaced protein Box Template with PBB Template for easy viewing. {{PBB|geneid=5327}} '''Tissue plasminogen activator''' (abbreviated '''tPA''' or '''PLAT''') is a [[serine protease]] normally found on the surface of endothelial cells of veins, capillaries, the pulmonary artery, heart, and uterus, and is secreted after vascular injury. It converts the [[proenzyme]] [[plasminogen]] to [[plasmin]], a [[fibrinolysis|fibrinolytic]] enzyme. Plasminogen is synthesized as a single chain, which is cleaved by tPA into the two chain disulfide linked [[plasmin]]. ==Function== This enzyme plays a role in [[cell migration]] and [[tissue remodeling]]. Increased enzymatic activity causes [[hyperfibrinolysis]], which manifests as excessive bleeding; decreased activity leads to [[hypofibrinolysis]] which can result in [[thrombosis]] or [[embolism]]. [[Image:Fibrinolysis.png|left|framed|Fibrinolysis (simplified). Blue arrows denote stimulation, and red arrows inhibition.]] ==Gene== [[Alternative splicing]] of the tPA [[gene]], ''tPA'', produces three [[transcript]]s. ==Clinical applications== [[Recombinant]] tPA is used in diseases that feature [[blood clot]]s, such as [[pulmonary embolism]], [[myocardial infarction]] and [[stroke]]. To be effective, tPA must be administered within the first three hours of the event to be given intravenously, or within six hours to be administered through an arterial catheter directly to the site of occlusion. The guideline in Ontario, Canada hospitals for ischemic strokes is that tPA must be given within 3 hours of the onset of symptoms. Because of this, only about 3% of patients qualify for this treatment. tPA appears to show benefit not only for large artery occlusions but also for [[lacunar stroke]]s. Since tPA dissolves [[blood clot]]s, there is risk of [[hemorrhage]] with its use. Recently tPA has been used to dissolve thrombi associated with ischemic strokes and brain injury. In addition, people with [[frostbite]] that were treated with tPA had fewer amputations than those that were not<ref>{{web cite|url=http://archsurg.ama-assn.org/cgi/content/abstract/142/6/546?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=Amalia+Cochran&searchid=1&FIRSTINDEX=0&resourcetype=HWCIT|title=Archives of Surgery}} <i>Reduction of the Incidence of Amputation in Frostbite Injury With Thrombolytic Therapy</i>, Bruen et al., 2007;142:546-553.</ref>. ==Further reading== {{refbegin | 2}} {{PBB_Further_reading | citations = *{{cite journal | author=Rijken DC |title=Relationships between structure and function of tissue-type plasminogen activator |journal=Klin. Wochenschr. |volume=66 Suppl 12 |issue= |pages= 33–9 |year= 1988 |pmid= 3126346 |doi= }} *{{cite journal | author=Bode W, Renatus M |title=Tissue-type plasminogen activator: variants and crystal/solution structures demarcate structural determinants of function |journal=Curr. Opin. Struct. Biol. |volume=7 |issue= 6 |pages= 865–72 |year= 1998 |pmid= 9434908 |doi= }} * Collen D, Billiau A, Edy J, De Somer P., Identification of the human plasma protein which inhibits fibrinolysis associated with malignant cells, Biochim Biophys Acta. 1977 Sep 29;499(2):194-201 *{{cite journal | author=Anglés-Cano E, Rojas G |title=Apolipoprotein(a): structure-function relationship at the lysine-binding site and plasminogen activator cleavage site |journal=Biol. Chem. |volume=383 |issue= 1 |pages= 93–9 |year= 2003 |pmid= 11928826 |doi= }} *{{cite journal | author=Ny T, Wahlberg P, Brändström IJ |title=Matrix remodeling in the ovary: regulation and functional role of the plasminogen activator and matrix metalloproteinase systems |journal=Mol. Cell. Endocrinol. |volume=187 |issue= 1-2 |pages= 29–38 |year= 2003 |pmid= 11988309 |doi= }} *{{cite journal | author=Teesalu T, Kulla A, Asser T, ''et al.'' |title=Tissue plasminogen activator as a key effector in neurobiology and neuropathology |journal=Biochem. Soc. Trans. |volume=30 |issue= 2 |pages= 183–9 |year= 2002 |pmid= 12023848 |doi= 10.1042/ |doi_brokendate=2008-06-21 }} *{{cite journal | author=Pang PT, Lu B |title=Regulation of late-phase LTP and long-term memory in normal and aging hippocampus: role of secreted proteins tPA and BDNF |journal=Ageing Res. Rev. |volume=3 |issue= 4 |pages= 407–30 |year= 2005 |pmid= 15541709 |doi= 10.1016/j.arr.2004.07.002 }} *{{cite journal | author=Sheehan JJ, Tsirka SE |title=Fibrin-modifying serine proteases thrombin, tPA, and plasmin in ischemic stroke: a review |journal=Glia |volume=50 |issue= 4 |pages= 340–50 |year= 2005 |pmid= 15846799 |doi= 10.1002/glia.20150 }} }} {{refend}} ==References== {{reflist}} ==See also== * [[Thrombolysis]] * [[Ultrasound-Enhanced Systemic Thrombolysis]] ==External links== * http://www.americanheart.org/presenter.jhtml?identifier=4751 * [http://www.sciam.com/article.cfm?chanID=sa004&articleID=00055D80-04DC-12D8-BDFD83414B7F0000 Widening the Window : Strategies to buy time in treating ischemic stroke] - Scientific American Magazine (August 2005) {{Coagulation}} {{Serine endopeptidases}} {{Antithrombotics}} [[Category:Hematology]] [[Category:Fibrinolytic system]] [[Category:EC 3.4.21]] {{hydrolase-stub}} [[de:Gewebespezifischer Plasminogenaktivator]] [[nl:Tissue plasminogen activator]] [[pt:Ativador do plasminogênio tecidual]] [[ru:Тканевной активатор плазминогена]] <!-- The PBB_Controls template provides controls for Protein Box Bot, please see Template:PBB_Controls for details. --> {{PBB_Controls | update_page = yes | require_manual_inspection = no | update_protein_box = yes | update_summary = no | update_citations = yes }}