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American Journal of Pathology, Vol 143, 949-958, Copyright © 1993 by American Society for Investigative Pathology
REGULAR ARTICLES |
WM Mars, R Zarnegar and GK Michalopoulos
Department of Pathology, University of Pittsburgh, Pennsylvania 15261.
Hepatocyte growth factor, also known as scatter factor, is a complete mitogen for hepatocytes that bears sequence and structural homology with plasminogen. Because it exists in both a mitogenically inactive single-chain form and an active two-chain form, we were interested in determining whether plasminogen activators could properly cleave single- chain hepatocyte growth factor to generate active two-chain hepatocyte growth factor. Herein we report that both urokinase-type plasminogen activator and tissue-type plasminogen activator can cleave single-chain hepatocyte growth factor, generating two-chain hepatocyte growth factor. When equal quantities of plasminogen activator-treated and activator-untreated hepatocyte growth factor are compared in serum-free in vitro bioassays, the treated hepatocyte growth factor is mitotically more active. Also, urokinase-type plasminogen activator was inactive against hepatocyte growth factor molecules with a mutated cleavage site. This suggests that urokinase-type and tissue-type plasminogen activator may be natural biological regulators of hepatocyte growth factor. Because the active form of hepatocyte growth factor is a powerful stimulator of DNA synthesis and cell motility, these findings may be relevant in understanding the role of plasminogen activators in the biology of cancer invasion and metastasis.
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L. Naldini, E. Vigna, A. Bardelli, A. Follenzi, F. Galimi, and P. M. Comoglio Biological Activation of pro-HGF (Hepatocyte Growth Factor) by Urokinase Is Controlled by a Stoichiometric Reaction J. Biol. Chem., January 13, 1995; 270(2): 603 - 611. [Abstract] [Full Text] [PDF]
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