PLG Gene

The PLG gene (PLG stands for "plasminogen") is a protein-coding gene located on chromosome 6q26. Compared to other mammals, the cluster of plasminogen-like genes to which this gene belongs is rearranged in catarrhal primates.

The plasminogen protein, an enzyme, encoded by the PLG gene is a serine protease that circulates as an inactive zymogen in blood plasma and is activated by various plasminogen activators such as:

• Tissue Plasminogen Activator (tPA).
• urokinase plasminogen activator (uPA)
• Kallikrein
• Factor XII (Hageman factor)

is converted into the active protease, plasmin. The conversion of plasminogen to plasmin involves cleavage of the peptide bond between Arg-561 and Val-562. Cleavage of plasmin also releases the protein angiostatin, which inhibits angiogenesis. Plasmin degrades many blood plasma proteins, including fibrin-containing blood clots. As a serine protease, plasmin cleaves fibrin as well as many other products such as fibronectin, thrombospondin, laminin, and von Willebrand factor.

Plasmin is inactivated by proteins such as alpha-2-macroglobulin and alpha-2-antiplasmin and by inhibitors of the various plasminogen activators. Plasminogen also interacts with plasminogen receptors, resulting in plasmin retention on cell surfaces and plasmin-induced cell signaling. Plasminogen localization to cell surfaces plays a role in extracellular matrix degradation,cell migration, inflammation, wound healing, oncogenesis, metastasis, myogenesis, muscle regeneration, neurite growth, and fibrinolysis. Plasminogen is also thought to play a role in acute respiratory distress syndrome (ARDS), which is caused in part by increased clot formation and suppression of fibrinolysis.

Plasmin dissolves the fibrin of blood clots and acts as a proteolytic factor in a variety of other processes, including embryonic development, tissue remodeling, tumor invasion, and inflammation. During ovulation, it weakens the walls of Graaf's follicle. It activates urokinase-type plasminogen activator, collagenases, and several complement zymogens such as C1 and C5. Cleavage of fibronectin and laminin leads to cell detachment and apoptosis. Also cleaves fibrin, thrombospondin and von Willebrand factor. Its role in tissue remodeling and tumor invasion can be modulated by CSPG4. Binds to cells. Angiostatin is an angiogenesis inhibitor that blocks neovascularization and growth of experimental primary and metastatic tumors in vivo.

Diseases associated with PLG include:

• Plasminogen deficiency type I (clinical picture = lignocellular conjunctivitis)

and

• Hereditary angioedema mutation in PLG . (see below Hereditary Angioedema 4).

1. Bateman JB et al.(1986) Ligneous conjunctivitis: an autosomal recessive disorder. J Pediat Ophthal Strabismus 23: 137-140.
2. Belbezier A et al. (2018) Plasminogen gene mutation with normal C1 inhibitor hereditary angioedema: three additional French families. (Letter) Allergy 73: 2237-2239.
3. Bork K et al. (2018) Hereditary angioedema with a mutation in the plasminogen gene. Allergy 73: 442-450.
4. Bouisson M (1847) Ophthalmie sur-aigue avec formation de pseudomembranes a la surface de la conjonctive. Ann Ocul (Paris) 17: 100-104.
5. Dewald G (2018) A missense mutation in the plasminogen gene, within the plasminogen kringle 3 domain, in hereditary angioedema with normal C1 inhibitor. Biochem Biophys Res Commun 498: 193-198.