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Protein kinase A phosphorylates and regulates dimerization of 14‐3‐3ζ
Author(s) -
Gu Young-Mi,
Jin Yun-Hye,
Choi Joong-Kook,
Baek Kwang-Hyun,
Yeo Chang-Yeol,
Lee Kwang-Youl
Publication year - 2006
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2005.12.024
Subject(s) - phosphorylation , threonine , serine , protein kinase a , chemistry , kinase , protein phosphorylation , microbiology and biotechnology , biochemistry , biology
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.