Casein kinase II is a negative regulator of c-Jun DNA binding and AP-1 activity

Cell. 1992 Sep 4;70(5):777-89. doi: 10.1016/0092-8674(92)90311-y.

Abstract

c-Jun, a major component of the inducible transcription factor AP-1, is a phosphoprotein. In nonstimulated fibroblasts and epithelial cells, c-Jun is phosphorylated on a cluster of two to three sites abutting its DNA-binding domain. Phosphorylation of these sites inhibits DNA binding, and their dephosphorylation correlates with increased AP-1 activity. We show that two of these sites, Thr-231 and Ser-249, are phosphorylated by casein kinase II (CKII). Substitution of the third site, Ser-243, by Phe interferes with phosphorylation of the inhibitory sites in vivo and by purified CKII in vitro. Microinjection into living cells of synthetic peptides that are specific competitive substrates or inhibitors of CKII results in induction of AP-1 activity and c-Jun expression. Microinjection of CKII suppresses induction of AP-1 by either phorbol ester or an inhibitory peptide. These results suggest that one of the roles of CKII, a major nuclear protein kinase with no known functions, is to attenuate AP-1 activity through phosphorylation of c-Jun.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Casein Kinase II
  • Cell Line
  • Down-Regulation
  • Enzyme Induction / drug effects
  • Molecular Sequence Data
  • Peptides / chemical synthesis
  • Peptides / pharmacology
  • Phosphorylation
  • Protein-Serine-Threonine Kinases / biosynthesis
  • Protein-Serine-Threonine Kinases / metabolism*
  • Proto-Oncogene Proteins c-jun / antagonists & inhibitors*
  • Proto-Oncogene Proteins c-jun / genetics
  • Trypsin

Substances

  • Peptides
  • Proto-Oncogene Proteins c-jun
  • Casein Kinase II
  • Protein-Serine-Threonine Kinases
  • Trypsin