tissue plasminogen activator

Plasminogen activator, tissue
PDB rendering based on 1a5h.
Available structures
1a5h, 1bda, 1pk2, 1pml, 1rtf, 1tpg, 1tpk, 1tpm, 1tpn
Identifiers
Symbols	PLAT; DKFZp686I03148; T-PA; TPA
External IDs	OMIM: 173370 MGI: 97610 HomoloGene: 717
Gene ontology Molecular function • peptidase activity • plasminogen activator activity Cellular component • extracellular region • extracellular space • cytoplasm • secretory granule • apical part of cell Biological process • protein modification process • proteolysis • blood coagulation • platelet-derived growth factor receptor signaling pathway
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	5327	18791
Ensembl	ENSG00000104368	ENSMUSG00000031538
UniProt	P00750	Q6P7U0
RefSeq	NM_000930 (mRNA)	NM_008872 (mRNA)
	NP_000921 (protein)	NP_032898 (protein)
Location	Chr 8: 42.15 - 42.18 Mb	Chr 8: 24.22 - 24.25 Mb
PubMed search	[1]	[2]

Tissue plasminogen activator (abbreviated tPA or PLAT) is a protein involved in the breakdown of blood clots. Specifically, it is a serine protease (EC 3.4.21.68) found on endothelial cells, the cells that line the blood vessels. As an enzyme, it catalyzes the conversion of plasminogen to plasmin, the major enzyme responsible for clot breakdown. Because it works on the clotting system, tPA is used in clinical medicine to treat only embolic or thrombolytic stroke. Use is contraindicated in hemorrhagic stroke and head trauma.

tPA may be manufactured using recombinant biotechnology techniques. tPA created this way may be referred to as recombinant tissue plasimogen activator or rtPA.

Function

A simplified illustration demonstrates clot breakdown (fibrinolysis), with blue arrows denoting stimulation, and red arrows inhibition.

The classic role of tPA is in the clotting system. Specifically, tPA catalyzes the conversion of plasminogen into plasmin. It does so by cleaving the single-chained plasminogen into two chains. These two chains are linked by a disulfide bond and the resulting molecule is called plasmin.

Increased enzymatic activity causes hyperfibrinolysis, which manifests as excessive bleeding. Decreased activity leads to hypofibrinolysis which can result in thrombosis or embolism.

Tissue plasminogen activator also plays a role in cell migration and tissue remodeling.

Genetics

Tissue plasminogen activator is a protein encoded by the PLAT gene, which is located on chromosome 8. The primary transcript produced by this gene undergoes alternative splicing, producing three distinct messenger RNAs.

Clinical applications

tPA is used in diseases that feature blood clots, such as pulmonary embolism, myocardial infarction and stroke, in a medical treatment called thrombolysis. 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.^{[citation needed]} Because of this, only about 3% of patients qualify for this treatment.^{[citation needed]} tPA appears to show benefit not only for large artery occlusions but also for lacunar strokes. Since tPA dissolves blood clots, there is risk of hemorrhage with its use.

Recently tPA has been used to dissolve thrombi associated with ischemic strokes and brain injury.^{[citation needed]}

In addition, people with frostbite who were treated with tPA had fewer amputations than those who were not.^[1]

In tPA overdose, aminocaproic acid works as an antidote.^[2]

Interactions

Tissue plasminogen activator has been shown to interact with Fibrinogen alpha chain,^[3][4] LRP1^[5][6] and SERPINI1.^[7]

See also

• Thrombolysis
• Ultrasound-Enhanced Systemic Thrombolysis
• Lyme disease

References

Further reading

v • d • e PDB Gallery 1a5h: CATALYTIC DOMAIN OF HUMAN TWO-CHAIN TISSUE PLASMINOGEN ACTIVATOR COMPLEX OF A BIS-BENZAMIDINE   1bda: CATALYTIC DOMAIN OF HUMAN SINGLE CHAIN TISSUE PLASMINOGEN ACTIVATOR IN COMPLEX WITH DANSYL-EGR-CMK (DANSYL-GLU-GLY-ARG CHLOROMETHYL KETONE)   1pk2: SOLUTION STRUCTURE OF THE TISSUE-TYPE PLASMINOGEN ACTIVATOR KRINGLE 2 DOMAIN COMPLEXED TO 6-AMINOHEXANOIC ACID AN ANTIFIBRINOLYTIC DRUG   1pml: KRINGLE-KRINGLE INTERACTIONS IN MULTIMER KRINGLE STRUCTURES   1rtf: COMPLEX OF BENZAMIDINE WITH THE CATALYTIC DOMAIN OF HUMAN TWO CHAIN TISSUE PLASMINOGEN ACTIVATOR [(TC)-T-PA]   1tpg: F1-G MODULE PAIR RESIDUES 1-91 (C83S) OF TISSUE-TYPE PLASMINOGEN ACTIVATOR (T-PA) (NMR, 298K, PH2.95, REPRESENTATIVE STRUCTURE)   1tpk: CRYSTAL STRUCTURE OF THE KRINGLE-2 DOMAIN OF TISSUE PLASMINOGEN ACTIVATOR AT 2.4-ANGSTROMS RESOLUTION   1tpm: SOLUTION STRUCTURE OF THE FIBRIN BINDING FINGER DOMAIN OF TISSUE-TYPE PLASMINOGEN ACTIVATOR DETERMINED BY 1H NUCLEAR MAGNETIC RESONANCE   1tpn: SOLUTION STRUCTURE OF THE FIBRIN BINDING FINGER DOMAIN OF TISSUE-TYPE PLASMINOGEN ACTIVATOR DETERMINED BY 1H NUCLEAR MAGNETIC RESONANCE

External links

• Tissue Plasminogen Activator from the American Heart Association
• Widening the Window : Strategies to buy time in treating ischemic stroke - Scientific American Magazine (August 2005)
• Study expands window for effective stroke treatment - explained on YouTube