Tissue plasminogen activator

Plasminogen activator, tissue
PDB rendering based on 1a5h.
Available structures: 1a5h, 1bda, 1pk2, 1pml, 1rtf, 1tpg, 1tpk, 1tpm, 1tpn
Identifiers
Symbol(s)	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
	Human	Mouse
Entrez	5327	18791
Ensembl	ENSG00000104368	ENSMUSG00000031538
Uniprot	P00750	Q6P7U0
Refseq	NM_000930 (mRNA) NP_000921 (protein)	NM_008872 (mRNA) 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 PLAT or tPA) 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 fibrinolytic enzyme. Plasminogen is synthesized as a single chain which is cleaved by PLAT 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.

Fibrinolysis (simplified). Blue arrows denote stimulation, and red arrows inhibition.

Gene

Alternative splicing of the PLAT gene, PLAT, produces three transcripts.

Clinical applications

Recombinant PLAT is used in diseases which feature blood clots, such as myocardial infarction and stroke. To be effective, PLAT 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 strokes. Since PLAT 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. Additionally, people with frostbite who were treated with tPA had fewer amputations than those who were not^[1].

Further reading

References

See also

• Thrombolysis
• Ultrasound-Enhanced Systemic Thrombolysis

External links

• http://www.americanheart.org/presenter.jhtml?identifier=4751
• Widening the Window : Strategies to buy time in treating ischemic stroke - Scientific American Magazine (August 2005)