Keratinocyte urokinase-type plasminogen activator is secreted as a single chain precursor.
Urokinase-type plasminogen activator (uPA) is produced and secreted by cultured human keratinocytes as a single chain precursor. UPA in keratinocyte conditioned medium is not susceptible to inhibition with diisopropylfluorophosphate (DFP), and it has an apparent molecular weight of 55 kD under both reducing and nonreducing conditions. Cleavage of keratinocyte uPA by plasmin results in the formation of a 96 kD complex comprised of activated uPA and PA inhibitor 2. PA extracted from normal human epidermis is only partially inhibited by DFP, suggesting that precursor uPA is also present in vivo. The synthesis of uPA as a precursor with reduced enzymatic activity as well as decreased affinity for inhibitors is likely to be a mechanism by which normal epidermis regulates plasminogen activation in vivo.
Hashimoto
K
K
Department of Dermatology, University of Pennsylvania School of Medicine, Philadelphia 19104.
Prystowsky
J H
JH
Baird
J
J
Lazarus
G S
GS
Jensen
P J
PJ
D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism*; D005341:Fibrinolysin / Q000494:pharmacology; D006801:Humans; D007531:Isoflurophate / Q000494:pharmacology; D008970:Molecular Weight; D010960:Plasminogen Activators / Q000096:biosynthesis / Q000378:metabolism*; D011498:Protein Precursors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis / Q000378:metabolism*
D011498:Protein Precursors; D007531:Isoflurophate; D010960:Plasminogen Activators; D005341:Fibrinolysin; D014568:Urokinase-Type Plasminogen Activator