The enigma PAI-2. Gene expression, evolutionary and functional aspects.

The type-2 plasminogen activator inhibitor (PAI-2) belongs to the ovalbumin subfamily of serpins. It exhibits close to 50% homology with several recently cloned protease inhibitors such as the leukocyte elastase inhibitor, the placental thrombin inhibitor and the squamous cell carcinoma antigen. PAI-2 exists in an intracellular, nonglycosylated form of 47 kDa and a secreted, glycosylated form of about 60 kDa. The PAI-2 gene does not have a signal peptide which might explain why the major portion of PAI-2 remains intracellularly. Several response elements have been identified in the promoter region which are necessary for constitutive and phorbol ester and retinoic acid induced expression of the gene. These include two AP-1 sites, and response elements for cAMP, glucocorticoids and retinoic acid. The physiological function of PAI-2 has not been clearly elucidated. It may have cytoprotective functions and appears to play a role in programmed cell death.