Assignment of tissue-type plasminogen activator to chromosome 8 in man and identification of a common restriction length polymorphism within the gene

The plasminogen activators (PAs) are serine proteinases which convert the inactive proenzyme plasminogen into plasmin, a proteinase associated with processes such as fibrinolysis and tissue remodelling. There are two immunologically distinct types of PA: tissue-type (t-PA), the main form involved in thrombolysis, and urokinase-type (u-PA), primarily involved in tissue degradation. Two or possibly more genes encode PA activity, and one locus has been provisionally assigned to chromosome 6 in man. We have isolated cDNA clones which encompass the entire coding sequence of the t-PA gene, and have used these to probe DNA on Southern blots isolated from 18 independent human-rodent somatic cell hybrid lines. The presence of the human gene for t-PA showed complete concordance with human chromosome 8 in the hybrids. In addition, the cDNA clones recognize a restriction fragment length polymorphism, where the two common alleles each have a frequency of approximately 0.5. t-PA and u-PA activities have been found in a wide variety of malignant cells, where they are thought to play a role in metastatic invasion of normal tissue. The results reported here will enable us to investigate whether genetic changes associated with the chromosome encoding t-PA are associated with altered t-PA expression in neoplasia.