Extracellular simian virus 40 induces an ERK/MAP kinase-independent signalling pathway that activates primary response genes and promotes virus entry

J Gen Virol. 1996 Sep;77 ( Pt 9):2173-82. doi: 10.1099/0022-1317-77-9-2173.

Abstract

Simian virus 40 (SV40) binding to growth-arrested cells activated an intracellular signalling pathway that induced the up-regulation of the primary response genes c-myc, c-jun and c-sis within 30 min and of JE within 90 min. The up-regulation of the primary response genes occurred in the presence of cycloheximide and when UV-inactivated SV40 was adsorbed to cells. SV40 binding did not activate Raf or mitogen-activated protein kinase (MAP/ERK1), or mobilize intracellular Ca2+. The SV40-induced up-regulation of c-myc and c-jun was blocked by the tyrosine kinase inhibitor, genistein, and by the protein kinase C (PKC) inhibitor, calphostin C, but not by expression of the MAP kinase-specific phosphatase, MKP-1. These results suggest that the SV40-induced signalling pathway includes the activities of a tyrosine kinase and a Ca(2+)-independent isoform of PKC, but not of Raf or MAP kinase. Finally, SV40 infectious entry into cells was specifically and reversibly blocked by genistein.

Publication types

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

MeSH terms

  • Animals
  • Calcium / metabolism
  • Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors
  • Calcium-Calmodulin-Dependent Protein Kinases / biosynthesis*
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • Cell Cycle Proteins*
  • Cell Line
  • Chlorocebus aethiops
  • Dual Specificity Phosphatase 1
  • Enzyme Inhibitors / pharmacology
  • Gene Expression Regulation, Viral*
  • Genistein
  • Humans
  • Immediate-Early Proteins / metabolism
  • Isoflavones / pharmacology
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases*
  • Naphthalenes / pharmacology
  • Phosphoprotein Phosphatases*
  • Platelet-Derived Growth Factor / genetics*
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C / metabolism
  • Protein Phosphatase 1
  • Protein Tyrosine Phosphatases / metabolism
  • Protein-Serine-Threonine Kinases / metabolism
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-jun / genetics*
  • Proto-Oncogene Proteins c-myc / genetics*
  • Proto-Oncogene Proteins c-raf
  • Proto-Oncogene Proteins c-sis
  • Signal Transduction*
  • Simian virus 40 / physiology*
  • Up-Regulation

Substances

  • Cell Cycle Proteins
  • Enzyme Inhibitors
  • Immediate-Early Proteins
  • Isoflavones
  • Naphthalenes
  • Platelet-Derived Growth Factor
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-jun
  • Proto-Oncogene Proteins c-myc
  • Proto-Oncogene Proteins c-sis
  • Genistein
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-raf
  • Protein Kinase C
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases
  • Phosphoprotein Phosphatases
  • Protein Phosphatase 1
  • DUSP1 protein, human
  • Dual Specificity Phosphatase 1
  • Protein Tyrosine Phosphatases
  • calphostin C
  • Calcium