Regulation of urokinase receptors in monocytelike U937 cells by phorbol ester phorbol myristate acetate.
A specific surface receptor for urokinase plasminogen activator (uPA) recognizes the amino-terminal growth factor-like sequence of uPA, a region independent from and not required for the catalytic activity of this enzyme. The properties of the uPA receptor (uPAR) and the localization and distribution of uPA in tumor cells and tissues suggest that the uPA/uPAR interaction may be important in regulating extracellular proteolysis-dependent processes (e.g., invasion, tissue destruction). Phorbol myristate acetate (PMA), an inducer of U937 cell differentiation to macrophage-like cells, elicits a time- and concentration-dependent increase in the number of uPAR molecules as shown by binding, cross-linking, and immunoprecipitation studies. The effect of PMA is blocked by cycloheximide. Overall, the data indicate that PMA increases the synthesis of uPA. PMA treatment also causes a decrease in the affinity of the uPAR for uPA, thus uncovering another way of regulating the interaction between uPA and uPAR. In addition, the PMA treatment causes a modification of migration of the cross-linked receptor in mono- and bidimensional gel electrophoresis.
Picone
R
R
International Institute of Genetics and Biophysics, CNR, Naples, Italy.
Kajtaniak
E L
EL
Nielsen
L S
LS
Behrendt
N
N
Mastronicola
M R
MR
Cubellis
M V
MV
Stoppelli
M P
MP
Pedersen
S
S
Danø
K
K
Blasi
F
F
D002452:Cell Count; D002460:Cell Line; D003432:Cross-Linking Reagents; D004591:Electrophoresis, Polyacrylamide Gel; D004792:Enzyme Precursors; D006801:Humans; D007163:Immunosorbent Techniques; D008970:Molecular Weight; D009000:Monocytes / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism; D010960:Plasminogen Activators / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000187:drug effects / Q000378:metabolism*; D055293:Receptors, Urokinase Plasminogen Activator; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
D003432:Cross-Linking Reagents; D004792:Enzyme Precursors; C524898:PLAUR protein, human; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D010960:Plasminogen Activators; D014568:Urokinase-Type Plasminogen Activator; D013755:Tetradecanoylphorbol Acetate