uPAR is composed of three Ly6/uPAR domains (D1–D3) that fold into a compact, “three-finger” architecture characteristic of the LU protein superfamily. These domains collectively form a high-affinity binding pocket for urokinase (uPA).

Unlike most receptors, uPAR lacks transmembrane and cytoplasmic segments, depending instead on lateral interactions with integrins and receptor tyrosine kinases (RTKs) to trigger downstream signaling cascades.

Schematic structure of uPAR showing the three-domain (D1–D3) organization and GPI-anchored membrane attachment. The diagram also illustrates urokinase binding and plasminogen activation localized at the cell surface.

The uPA/uPAR system operates as a surface-bound catalytic unit:

1. Step 1: uPAR captures pro-uPA or active uPA on the cell membrane.
2. Step 2: uPA converts plasminogen to plasmin, which degrades ECM proteins.
3. Step 3: The resulting proteolytic fragments and growth factors promote cell movement, tissue remodeling, and signaling.

Even beyond proteolysis, uPAR participates in non-enzymatic signaling by coupling with β1/β3 integrins, EGFR, and vitronectin, promoting cell adhesion, migration, and epithelial-mesenchymal transition (EMT). This makes it a key factor in both cancer progression and tissue repair.

Cancer Invasion and Metastasis

Overexpression of uPAR has been documented in numerous cancers — breast, prostate, glioblastoma, and colorectal — correlating with tumor aggressiveness and metastatic potential. Imaging studies using uPAR-specific probes show how receptor density correlates with invasive front regions of tumors.

Immunofluorescence image showing uPAR localization in cancer cells. Co-staining with actin cytoskeleton (red) and uPAR (green) demonstrates enrichment at invasive protrusions, consistent with its role in matrix degradation and motility.

This dual role—anchoring enzymatic activity and coordinating migration—makes uPAR a potent biomarker and therapeutic target. Blocking uPAR–uPA interactions has shown promise in preclinical models by reducing invasion and angiogenesis.

Inflammation, Fibrosis, and suPAR as a Biomarker

The soluble form of uPAR (suPAR), released upon proteolytic cleavage, circulates in plasma and serves as a marker for immune activation and tissue injury. Elevated suPAR levels are linked to chronic inflammation, renal failure, cardiovascular disease, and fibrosis progression.

In nephrology, suPAR has emerged as a predictive biomarker for glomerular injury and podocyte dysfunction.

The availability of recombinant human uPAR proteins enables a variety of cutting-edge experimental approaches:

1. Ligand-binding studies: Quantifying affinity between uPAR and uPA via SPR, ELISA, or fluorescence assays.
2. Inhibitor screening: Testing peptides or antibodies designed to block the uPA–uPAR interface.
3. Cell migration assays: Measuring the impact of uPAR overexpression or inhibition on motility.
4. Structural and imaging studies: Using recombinant uPAR to resolve 3D structures or as a target for fluorescent tracers.

Researchers using GenPrice’s Human uPAR Protein can verify its suitability for binding and inhibition assays, ensuring biologically active conformation and purity above 95%.

The Human Plasminogen Activator, Urokinase Receptor (uPAR) is far more than a surface anchor for proteases—it’s a multifunctional signaling hub bridging the extracellular matrix, cell adhesion, and immune communication.

Studying uPAR using validated recombinant proteins, such as those offered by GenPrice, provides invaluable insights into molecular mechanisms underlying cancer, inflammation, and tissue regeneration.

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