Protein kinase A phosphorylates and regulates dimerization of 14-3-3ζ

Young Mi Gu, Yun Hye Jin, Joong Kook Choi, Kwang Hyun Baek, Chang Yeol Yeo, Kwang Youl Lee

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59 Scopus citations


Recognition of phosphorylated serine/threonine-containing motifs by 14-3-3 depends on the dimerization of 14-3-3. However, the molecular cues that control 14-3-3 dimerization are not well understood. In order to identify proteins that control 14-3-3 dimerization, we analyzed proteins that have effects on 14-3-3 dimerization and report that protein kinase A (PKA) phosphorylates 14-3-3ζ at a specific residue (Ser58). Phosphorylation by PKA leads to modulation of 14-3-3ζ dimerization and affect its interaction with partner proteins. Substitution of Ser58 to Ala completely abolished phosphorylation of 14-3-3ζ by PKA. A phospho-mimic mutant of 14-3-3ζ, Ser58 to Glu substitution, failed to form homodimers, showed reduced interaction with 14-3-3ε and p53, and could not enhance transcriptional activity of p53. Moreover, activation of PKA decreases and inhibition of PKA increases the dimerization of 14-3-3ζ and the functional interaction of 14-3-3ζ with p53. Therefore, our results suggest that PKA is a new member of protein kinases that can phosphorylate and impair the function of 14-3-3.

Original languageEnglish
Pages (from-to)305-310
Number of pages6
JournalFEBS Letters
Issue number1
StatePublished - 9 Jan 2006

Bibliographical note

Funding Information:
This work is supported to by a grant to C.-Y.Y. [C00175 (R08-2003-000-10943-0)] from the Korea Research Foundation and by the Ewha Womans University Research Grants 2003 to C.-Y.Y.


  • 14-3-3ζ
  • Dimerization
  • Phosphorylation
  • Protein kinase A


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