Cell-surface plasminogen receptor (Plg-R)

Cell-surface plasminogen receptors (Plg-Rs) are a heterogeneous class of membrane-bound proteins and glycoproteins that facilitate the localization and activation of plasminogen on the cell surface. These receptors, which include specific entities such as Plg-RKT, Annexin A2, and alpha-enolase, typically utilize C-terminal lysine residues to bind the kringle domains of plasminogen. This binding significantly accelerates the conversion of the zymogen plasminogen into the active serine protease plasmin by activators like urokinase-type plasminogen activator (uPA) and tissue-type plasminogen activator (tPA). In mesenchymal stem cells (MSCs), these membrane glycoproteins are vital for pericellular proteolysis, a process essential for cell migration, tissue remodeling, and the mobilization of stem cells from the bone marrow. The plasminogen receptor system is a key therapeutic target in conditions involving excessive fibrinolysis or pathological cell invasion, such as cancer metastasis and inflammatory diseases. Drugs like tranexamic acid and aminocaproic acid act as lysine analogs that competitively inhibit the binding of plasminogen to these receptors, effectively halting the generation of plasmin and its subsequent proteolytic activities. Understanding the specific expression and function of these receptors on MSCs provides insights into their role in the tumor microenvironment and their potential as targets for modulating stem cell behavior in regenerative medicine.

Other names

Plasminogen-binding proteinMSC membrane glycoproteinsPlasminogen receptor with a C-terminal lysine (Plg-RKT)Annexin A2Alpha-enolase (ENO1)S100A10Histone H2BCytokeratin 8

Antifibrinolytic drugs such as tranexamic acid and aminocaproic acid act as lysine analogs that bind to the kringle domains of plasminogen. This binding competitively inhibits the interaction between plasminogen and the C-terminal lysine residues of cell-surface plasminogen receptors, preventing the localization and accelerated activation of plasminogen into the active protease plasmin on the cell membrane.