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Background
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UPA is a serine protease with an extremely limited substrate specificity, cleaving the sequence Cys-Pro-Gly-Arg560-Val561-Val-Gly-Gly-Cys in plasminogen to form plasmin. uPA is a potent marker of invasion and metastasis in a variety of cancers associated with breast, stomach, colon, bladder, ovary, brain and endometrium. For example, the combination (both low vs. either or both high) of uPA and its inhibitor, plasminogen activator inhibitor-1 (PAI-1), outperforms the single factors as well as other traditional prognostic factors with regard to risk group assessment for breast cancer, particularly in node-negative breast cancer. The uPA is initially synthesized as 431 amino acid precursor with a N-terminal signal peptide (20 residues). The single chain molecule is processed into a disulfide-linked two-chain molecule. The B chain starting at Ile179 corresponds to the catalytic domain. Two forms of the A chain exist, one starting at Ser21 (the long form) and the other at Lys156 (the short form). The resulting two-chain forms have different molecular weights (MW). The B chain is common for both forms whereas the long and short A chains are unique to the high and low MW forms, respectively. The long A chain contains an EGF-like domain, which is responsible for binding of the uPA receptor (uPAR). Both high and low MW forms exist in the purified recombinant Rabbit uPA.
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