Disease relevance of PLAU

• Inhibition of uPA activity with natural (plasminogen activator inhibitor-1) or synthetic (amiloride) inhibitors diminished HT-hi/diss Matrigel invasion in vitro and intravasation and metastasis in vivo [1].

High impact information on PLAU

• We have previously established that Hox D3 is required for expression of integrin alphavbeta3 and urokinase plasminogen activator (uPA), which contribute to EC adhesion, invasion, and migration during angiogenesis [2].
• Activity-based protein profiling revealed multiple serine hydrolases with altered activity between HT-hi/diss and HT-lo/diss cells, with the largest difference being the activity of urokinase-type plasminogen activator (uPA) [1].
• To analyze the role of uPA activity specifically in the process of intravasation, we grafted cells from the two HT-1080 variants onto the chorioallantoic membrane of chick embryos and measured levels of tumor cell intravasation in the distal chorioallantoic membrane using quantitative human-specific Alu PCR [1].
• However, the sequence of the chicken uPA gene is similar to the mammalian uPA genes only within the protein-coding portions of exons [3].
• The chicken urokinase-type plasminogen activator (uPA) cDNA and gene have been isolated and the complete nucleotide sequence of each established. cDNA sequence and Northern blot RNA analysis indicate that the chicken uPA mRNA is approximately 2500 nucleotides in size and contains a large 3'-noncoding region (998 nucleotides) [3].

Biological context of PLAU

• The chicken uPA gene is similar to the mammalian uPA genes in both size (8158 base pairs between transcription initiation and polyadenylation sites) and organization (11 exons) [3].
• The predicted amino acid sequence of the chicken uPA primary translation product (434 residues) suggests a domain architecture comparable to the mammalian uPA proteins with the form: (i) signal peptide, (ii) growth factor domain (GF), (iii) kringle domain (K), and (iv) serine protease domain (C) [3].
• In addition, the higher levels of uPA mRNA found in granulosa cells actively undergoing apoptosis and in follicles most susceptible to atresia (4-8 mm) suggest a role for this protease in mediating processes both during the early stages of programmed cell death and in the later stages of follicle atresia and resorption [4].
• The aim of the present study was to examine the regulatory role of transforming growth factor alpha (TGF alpha) on urokinase plasminogen activator (uPA) gene expression and protein levels in hen granulosa cells from different stages of ovarian follicular development in vitro [5].
• We speculate that VX-2 cells release uPA to activate fibrinolysis within the tumor stroma [6].

Anatomical context of PLAU

• Hen granulosa cells produce a uPA with a molecular mass of about 35 kDa and a transcript size of approximately 2.5 kb [5].

Analytical, diagnostic and therapeutic context of PLAU

• The uPA mRNA abundance and protein content were determined by Northern and Western blot analysis, respectively [5].

References