T5600-10J

Sheep Anti-TPA (Tissue-type Plasminogen Activator, t-plasminogen Activator, t-PA, tPA, INN=Alteplase, INN=Reteplase, Tissue-type Plasminogen Activator Chain A, Tissue-type Plasminogen Activator Chain B, PLAT)

PLAT (Plasminogen activator; also tPA/Tissue Plasminogen Activator) is a 64-69kD extracellular glycoprotein that belongs to the peptidase S1 family of enzymes. It is secreted by diverse cell types such as fibroblasts, endothelial cells and astrocytes. Unlike many other serine proteases, PLAT/tPA circulates as an active proenzyme. Following clot formation, both tPA and its substrate, plasminogen, bind to clot fibrin. Here, tPA converts plasminogen to plasmin, an enzyme that subsequently degrades the fibrin matrix of the clot. Plasmin also cleaves local tPA, generating a disulfide-linked, two chain tPA isoform whose activity is potentiated 5 to10 fold relative to the uncleaved form. tPa also cleaves PDGFCC and activates MMP9, suggesting an expanded role in vascular remodeling. Human PLAT/tPA is secreted as a 530aa single chain polypeptide (aa33-562). Depending upon its source, aa33-35 or aa33-38 may be removed in the circulation. PLAT contains one N-terminal fibronectin type I region (aa39-81), an EGD-like domain (aa82-120) a two kringle structures (127-208; 215-296) and a peptidase S1 domain (aa311-561). Plasmin cleaves PLAT/tPA between aa310-311, generating an active disulfide- linked heterodimeric molecule that contains chains of 35kD and 33kD, respectively. There are multiple isoform variants. One contains a three aa substitution for aa140 coupled to a deletion of aa79-208, a second shows a Gly substitution for aa39-85, and a third possesses a 23aa substitution for aa269-562. Two additional isoforms shows a His substitution for aa54-134, and a 25aa substitution for aa269-562, respectively. Over aa36-562, human PLAT shares 81% aa sequence identity with mouse PLAT.