Definition

Urokinase plasminogen activator surface receptor (uPAR), also known as urokinase receptor or CD87 (differentiation cluster 87), is a protein encoded by the PLAUR gene in the human body. It is a multidomain glycoprotein anchored to the cell membrane by glycosylphosphatidylinositol (GPI). uPAR is a high-affinity receptor for urokinase-type plasminogen activator (uPA, also known as PLAU) that is anchored to cell membranes via GPI. Urokinase plasminogen activator receptor (uPAR) is a uPA specific receptor, a highly glycosylated single-chain glycoprotein composed of 313 amino acids with a molecular weight of 50-60 kD, and is available in membrane and soluble types. uPAR is widely present in a variety of cells, the most abundant on monocytes, others such as polymorphonuclear cells, vascular endothelial cells, smooth muscle cells, fibroblasts, and suPAR in plasma. Vascular cytokines promote uPAR expression on epithelial cells via protein kinase C. Metallomatrice-protease hydrolyzed uPAR. The extracellular region includes the D1, D2, and D3 domains, and the D1-D2 junction can be sheared to produce D1 and D2-D3, where D1 alone can also bind to uPA, but the affinity decreases at least 1500 times when the intact uPAR binds. D2-D3 has the same chemotaxis characteristics as uPA and can bind to the GPCR protein FPRL1 to transmit chemotaxis signals. uPAR can also be detached from the membrane as a whole, forming soluble suPAR, a soluble form that is thought to be an indicator of tumor prognosis. uPA, which is a ligand, is initially an inactive enzyme pro-uPA, which can be activated upon binding to uPAR to form a double-stranded structure with active disulfide bonds.

Fig. 1 Structure of protein PLAUR. Based on PyMOL rendering of PDB 1YWH. 

Fig. 2 Molecular Structural of the uPA 

Function

Tumor makers: Soluble urokinase plasminogen activator receptor (suPAR) has been found to be a biomarker of inflammation. Elevated suPAR is seen in chronic obstructive pulmonary disease, asthma, liver failure, heart failure, cardiovascular disease, and rheumatoid arthritis.

Regulates plasmin formation: uPAR has a high affinity with uPA. After uPA binds to its receptor, it activates plasminogen bound to the cell surface and dissolves fibrin. This plasmin binding on the cell surface can be protected to a certain extent from α2-PI, but uPA bound to the cell membrane can still be inhibited by PAI-l and PAI-2.uPAR is part of the plasminogen activation system and is involved in tissue restructuring events in healthy bodies, such as breast degeneration and wound healing. In order to be able to reorganize tissue, the old tissue must be able to be degraded. An important mechanism of this degradation is the proteolytic cascade initiated by the plasminogen activation system. uPAR binds urokinase, thereby limiting plasminogen activation to near cell membranes. When urokinase binds to the receptor, a cleavage occurs between the GPI anchor and uPAR, releasing a soluble form of protein called suPAR.

Cell adhesion and movement: Through fibrinolysis on the cell surface, uPAR can degrade the cell matrix and play an important regulatory role in cell adhesion and movement, and uPAR has a chemochemotaxis effect on monocytes. At the same time, after binding to ligands, uPA coordinates with integrins, transmits signals, activates protein kinase C, G proteins and other pathways, and finally activates protein kinases and extracellular signal-regulatory kinases through cell splitting agents, affecting cell adhesion and migration.
Clinical Application

Tumor Genes

In gene therapy targeting the uPA-uPAR system, antisense oligonucleotide (aODN) technology, RNA interference (RNAi) technology and aptamer technology are more mature solutions. Since the uPA-uPAR system has the effect of promoting tumor invasion and metastasis, the uPAR-aODN constructed by Anna et al. inhibits the epithelial-mesenchymal transformation process of melanoma by inhibiting TGF-β, thereby slowing down tumor progression. At the same time, the aODN targeting cyclooxygenase-2 constructed by Wu et al. inhibits the invasion of human osteosarcoma cells by indirectly inhibiting the transcription of uPA and uPAR.

Tumor Drugs

Compared with traditional chemotherapy drugs, peptide drugs have significant advantages such as high targeting, low toxicity, low immunogenicity and low preparation cost in the treatment of tumors, so peptide drugs have unique advantages in targeted therapy of tumors. Because uPAR lacks transmembrane regions and intracellular domains, its mediated cell signal transduction relies on integrins and Vitronection, which requires protein-protein interaction (PPI), and the binding of uPA to uPAR also requires PPI, which lays the foundation for peptide drugs to treat tumors by targeting the uPA-uPAR system.

Tumor Immunity

Since uPAR is both a membrane protein and is significantly highly expressed in a variety of tumor tissues, this makes it a new target for tumor immunotherapy. Inhibitors of various components of the plasminogen activation system have been sought as possible anticancer drugs.

 Fig. 3 Graphic representation of the uPAR system on cell surface.

Alpha Lifetech Inc. is dedicated to developing uPAR diagnostic regents. Alpha Lifetech Inc. is a reputable supplier focusing on research, manufacture and sales of In Vitro Diagnostic (IVD) regents. All the IVD regents offered by Alpha Lifetech Inc. have undergone strict QC validation and are certified by the COA (certificate of analysis). Meanwhile, we can provide customized services according to customers' requirements. Alpha Lifetech Inc. is committed to supply high-quality, high-sensitivity antigen and antibody products for scientific research and industrial customers. In addition to regular small packages, Alpha Lifetech Inc.'s large-scale fermentation platform also allows us to provide raw material-grade IVD regents for the majority of industrial customers.

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