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Development, Vol 119, Issue 1 191-198, Copyright © 1993 by Company of Biologists
JOURNAL ARTICLES |
PM Carroll, WG Richards, AL Darrow, JM Wells and S Strickland
Department of Pharmacology, State University of New York at Stony Brook 11794-8651.
The serine protease tissue-plasminogen activator (t-PA) has previously been shown to be intracellular in mouse secondary oocytes and extracellular in fertilized eggs. Here we demonstrate that extracellular t-PA activity is bound to the surface of the fertilized egg. The level of t-PA activity associated with preimplantation mouse embryos decreases in the 2-cell stage embryo, then increases in 4-cell and morula stage embryos. However, morulae grown in culture from fertilized eggs lack t-PA activity but are able to bind exogenously added mouse t-PA. Additionally, northern analysis indicates that preimplantation embryos do not contain detectable levels of t-PA mRNA. Therefore, the enzyme activity associated with 4-cell and morula stage embryos in vivo is derived from t-PA present in the oviduct lumen that binds the embryo, and not from protein produced from translation of embryonic mRNA. The binding activity is species and protein specific in that neither mouse urokinase-type plasminogen activator (u-PA) nor human t-PA bind to cultured morulae. Furthermore, binding activity is dose-dependent and saturable, and does not require the active site of t-PA. These data indicate that a cell surface-specific t-PA-binding activity exists in the preimplantation mouse embryo and may localize function and concentrate the proteolytic activity of t-PA in early mouse development.
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J. Wells and S Strickland Aprotinin, a Kunitz-type protease inhibitor, stimulates skeletal muscle differentiation Development, January 12, 1994; 120(12): 3639 - 3647. [Abstract] [PDF]
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P. Carroll, S. Tsirka, W. Richards, M. Frohman, and S Strickland The mouse tissue plasminogen activator gene 5' flanking region directs appropriate expression in development and a seizure-enhanced response in the CNS Development, January 11, 1994; 120(11): 3173 - 3183. [Abstract] [PDF]
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