Human Mast Cell Tryptase Activates Single-Chain Urinary-Type Plasminogen Activator (Pro-Urokinase)

Document Type

Article

Publication Date

4-1-1994

Description

Human lung mast cell tryptase is a trypsin-like serine proteinase that is stored in mast cell granules and released by activated mast cells. Here we report that mast cell tryptase is a potent activator of single-chain urinary- type plasminogen activator (scu-PA, or pro-urikinase), the zymogen form of urinary-type plasminogen activator (u-PA). Activation was complete within 75 min using an enzyme:substrate molar ratio of 1:50 and was accompanied by cleavage of scu-PA at Lys158-Ile159, generating active two-chain u-PA. The reaction was dependent on enzyme concentration and obeyed Michaelis- Menten kinetics. Kinetic constants calculated for scu-PA activation by mast cell tryptase are K(m) = 34 μM, V(max) = 3.6 pmol of u-PA/min, and k(cat) = 0.08 s-1. These data suggest that tryptase from tumor-associated mast cells may participate in the activation of scu-PA.

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