suPAR and its ligand are involved in numerous physiological and pathological pathways, which include the plasminogen activating pathway, regulation of pericellular proteolysis, modulation of cell adhesion, migration and proliferation through interactions with proteins present in the extracellular matrix4.
The involvement of the soluble form of the receptor in the inflammation process is well documented although the actual biological function of the molecule is still not clear. Studies suggest that suPAR is a regulator of uPAR/uPA actions through competitive inhibition of uPAR and several studies conclude that the cleaved receptor is a chemotactic agent promoting the immune response.3
“it is essential to have the help of biomarkers, such as suPAR, which can support the discharge decision”
Juan González del Castillo, Dr PhD, Hospital Clínico San Carlos, Spain
suPAR News Vol. 1, April 2019
In April 2006, the crystal structure of suPAR was published in Science. The three-domain structure was shown to be able to differentially rotate around its main axis to accommodate a number of complex ligands1.
Due to this ability to change conformation, suPAR demonstrates a highly variable binding pocket, which is believed to explain its immense value in a number of different functions including cell signaling, cell migration, and immune response.
Amongst other functions, the receptor for urokinase plasminogen activator (uPAR) promotes invasion by neoplastic or inflammatory cells by focusing proteolysis of urokinase to the cell surface. In pathologic conditions, soluble forms of the receptor (suPAR) are released and activate cell receptors to promote chemotaxis and immune response.
It has also been published that no genetic polymorphisms exist causing humans to naturally express high levels of suPAR 2, indicating that elevated concentrations of suPAR can be attributed to immune activation or immune response to a specific challenge. Further scientific data strengthen the conclusion that – independent of infection type – elevated blood levels of suPAR carry a strong negative prognostic value for the respective disease condition.
The urokinase plasminogen activator receptor (uPAR) is expressed on immune cells, in particular on monocytes and activated T-cells and involved in several immune functions including migration, adhesion, angiogenesis, fibrinolysis and cell proliferation. The shedding of uPAR from the cell surface generates soluble uPAR (suPAR), a highly flexible pro-inflammatory molecule with intrinsic chemotactic properties4.
1: Xu X et al., Crystal structure of the urokinase receptor in a ligand-free form J Mol Biol. 2012 Mar 9;416(5):629-41.
2: Schneider UV et al., The prognostic value of the suPARnostic ELISA in HIV-1 infected individuals is not affected by uPAR promoterpolymorphisms, BMC Infect Dis. 2007 Nov 16;7:134
3. Huai Q, et al. Structure of human urokinase plasminogen activator in complex with its receptor, Science. 2006 Feb 3;311(5761):656-9.
4. Thunø M et al., suPAR: the molecular crystal ball, Dis Markers. 2009;27(3):157-72.