Protein kinase A phosphorylates and regulates dimerization of 14-3-3 epsilon.
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.
Mesh Terms:
14-3-3 Proteins, Amino Acid Motifs, Amino Acid Substitution, Cell Line, Cyclic AMP-Dependent Protein Kinases, Dimerization, Enzyme Activation, Humans, Phosphorylation, Point Mutation, Protein Binding, Protein Processing, Post-Translational, Tumor Suppressor Protein p53
14-3-3 Proteins, Amino Acid Motifs, Amino Acid Substitution, Cell Line, Cyclic AMP-Dependent Protein Kinases, Dimerization, Enzyme Activation, Humans, Phosphorylation, Point Mutation, Protein Binding, Protein Processing, Post-Translational, Tumor Suppressor Protein p53
FEBS Lett.
Date: Jan. 09, 2006
PubMed ID: 16376338
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