Protein kinase A phosphorylates and regulates dimerization of 14-3-3 epsilon.
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Gu YM, Jin YH, Choi JK, Baek KH, Yeo CY, Lee KY
Protein kinase A phosphorylates and regulates dimerization of 14-3-3 epsilon.
FEBS Lett. 2006 Jan 9;580(1):305-10. Epub 2005 Dec 19.
- PubMed ID
- 16376338 [ View in PubMed]
- Abstract
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 14-3-3zeta at a specific residue (Ser58). Phosphorylation by PKA leads to modulation of 14-3-3zeta dimerization and affect its interaction with partner proteins. Substitution of Ser58 to Ala completely abolished phosphorylation of 14-3-3zeta by PKA. A phospho-mimic mutant of 14-3-3zeta, Ser58 to Glu substitution, failed to form homodimers, showed reduced interaction with 14-3-3epsilon and p53, and could not enhance transcriptional activity of p53. Moreover, activation of PKA decreases and inhibition of PKA increases the dimerization of 14-3-3zeta and the functional interaction of 14-3-3zeta 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.