Phorbol ester induces the biosynthesis of glycosylated and nonglycosylated plasminogen activator inhibitor 2 in high excess over urokinase-type plasminogen activator in human U-937 lymphoma cells

J Cell Biol. 1987 Mar;104(3):705-12. doi: 10.1083/jcb.104.3.705.


The tumor-promoting phorbol ester PMA induces changes in the histiocytic human lymphoma cell line U-937 akin to cellular differentiation (Ralph, P., N. Williams, M. A. S. Moore, and P. B. Litcofsky, 1982, Cell. Immunol., 71:215-223) and concomitantly stimulates the biosynthesis of plasminogen activator inhibitor 2 (PAI 2) and of urokinase-type plasminogen activator (u-PA). PAI 2 is found in a nonglycosylated intracellular and a glycosylated secreted form. The former appears to be identical to PAI 2 previously purified from placental extracts and large-scale U-937 cell cultures. The sixfold increase of PAI 2 antigen measured 24 h after PMA treatment in cell extracts and conditioned media is accompanied by an equal increase of active PAI 2 mRNA, whereas the 6 to 13-fold increase of u-PA antigen in the same samples is associated with only a 1.5-fold mRNA increase. The increase of PAI 2, but not of u-PA, biosynthesis requires transcription. A 50-fold molar excess of PAI 2 over u-PA is found in both extracts and conditioned media of PMA-treated cells. PAI 2 represents at least 0.3% of total de novo synthesized protein 24 h after induction with PMA. Thus, PAI 2, but not u-PA, is an abundant product of this precursor analogue of the mononuclear phagocyte lineage, and might represent a new marker for monocyte/macrophage differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation / drug effects
  • Cell Line
  • Glycoproteins / biosynthesis*
  • Glycoproteins / genetics
  • Humans
  • Kinetics
  • Lymphoma, Large B-Cell, Diffuse
  • Methionine / metabolism
  • Plasminogen Activators / antagonists & inhibitors
  • Plasminogen Inactivators
  • Protein Biosynthesis
  • Sulfur Radioisotopes
  • Tetradecanoylphorbol Acetate / pharmacology*
  • Urokinase-Type Plasminogen Activator / biosynthesis*
  • Urokinase-Type Plasminogen Activator / genetics


  • Glycoproteins
  • Plasminogen Inactivators
  • Sulfur Radioisotopes
  • Methionine
  • Plasminogen Activators
  • Urokinase-Type Plasminogen Activator
  • Tetradecanoylphorbol Acetate