The native one-chain tissue plasminogen activator from the human melanoma cell line (Bowes) occurs in two variants as demonstrated by sodium dodecylsulphate—polyacrylamide gel electrophoresis of reduced and carboxymethylated samples. The two variants were isolated by affinity chromatography on arginine—Sepharose using a guanidinium—HCl gradient. in the order of elution, the variants were designated tissue plasminogen activator I and II. Variant I was found to be 3000 M r larger than variant II and the difference was found to reside in the N-terminal half of the molecule. No substantial difference in carbohydrate content nor in enzymatic activity was demonstrated.
