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

Authors
  • Lin, A
  • Frost, J
  • Deng, T
  • Smeal, T
  • al-Alawi, N
  • Kikkawa, U
  • Hunter, T
  • Brenner, D
  • Karin, M
Type
Published Article
Journal
Cell
Publisher
Elsevier
Publication Date
Sep 04, 1992
Volume
70
Issue
5
Pages
777–789
Identifiers
PMID: 1516134
Source
Medline
License
Unknown

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.

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