Regulation of urokinase-type plasminogen activator expression by the v-mos oncogene

Oncogene. 1995 Dec 21;11(12):2639-48.


We undertook a study to determine if the serine-threonine kinase-encoding v-mos oncogene regulated the expression of the urokinase-type plasminogen activator. An expression vector encoding v-mos, but not a kinase-inactive mutant, stimulated urokinase promoter activity in CAT assays employing a squamous cell carcinoma cell line. The induction of urokinase promoter activity by v-mos was mediated, in part, via an increased AP-1 activity since (a) mutation of 2 AP-1 binding sites (at -1967 and -1885), or the co-expression of a transactivation domain-lacking c-jun mutant reduced the induction of the urokinase promoter by v-mos and (b) expression of v-mos increased the activity of a CAT reporter driven by three AP-1 tandem repeats. The stimulation of the urokinase promoter by v-mos was partially countered by co-expression of an ERK1/ERK2-inactivating phosphatase. Western blotting and zymographic analysis indicated that v-mos-transformed NIH3T3 cells (MSV NIH-3T3) secreted more urokinase compared with NIH3T3 cells and this was associated with a higher level of activated ERK1 and ERK2. Expression of a catalytically-inactive MAPKK mutant reduced the activity of a urokinase promoter-driven CAT reporter in the MSV NIH-3T3 cells. In conclusion, the data herein indicate that urokinase expression is regulated by v-mos through a MAPKK-dependent signaling pathway.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3T3 Cells
  • Animals
  • Base Sequence
  • Binding Sites
  • Gene Expression Regulation, Enzymologic*
  • Humans
  • Mice
  • Mitogen-Activated Protein Kinase Kinases
  • Molecular Sequence Data
  • Oncogene Proteins v-mos / genetics*
  • Oncogenes*
  • Promoter Regions, Genetic
  • Protein Kinases / physiology
  • Transcription Factor AP-1 / metabolism
  • Transfection
  • Tumor Cells, Cultured
  • Urokinase-Type Plasminogen Activator / genetics*


  • Oncogene Proteins v-mos
  • Transcription Factor AP-1
  • Protein Kinases
  • Mitogen-Activated Protein Kinase Kinases
  • Urokinase-Type Plasminogen Activator