The Dimeric Versus Monomeric Status of 14-3-3ζ Is Controlled by Phosphorylation of Ser58 at the Dimer Interface
| Autor: | Joanna M. Woodcock, Jane E. Murphy, Angel F. Lopez, Michael C. Berndt, Frank C. Stomski |
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| Rok vydání: | 2003 |
| Předmět: |
Tyrosine 3-Monooxygenase
Protein Conformation Amino Acid Motifs Immunoblotting Apoptosis Plasma protein binding Biology Biochemistry Serine Mice Protein structure Animals Phosphorylation Molecular Biology Mice Inbred BALB C Phosphopeptide Kinase Cell Biology Phosphoserine Motif Recombinant Proteins Cross-Linking Reagents 14-3-3 Proteins NIH 3T3 Cells Biophysics Electrophoresis Polyacrylamide Gel Rabbits Signal transduction Dimerization Protein Binding Signal Transduction |
| Zdroj: | Journal of Biological Chemistry. 278:36323-36327 |
| ISSN: | 0021-9258 |
| Popis: | The 14-3-3 proteins play a central role in the regulation of cell growth, cycling, and apoptosis by modulating the functional activities of key signaling proteins. Through binding to a phosphoserine motif, 14-3-3 alters target proteins activities by sequestering them, relocalizing them, conformationally altering their functional activity, or by promoting interaction with other proteins. These functions of 14-3-3 are facilitated by, if not dependent on, its dimeric structure. We now show that the dimeric status of 14-3-3 is regulated by site-specific serine phosphorylation. We found that a sphingosine-dependent kinase phosphorylates 14-3-3 in vitro and in vivo on a serine residue (Ser58) located within the dimer interface. Furthermore, by developing an antibody that specifically recognizes 14-3-3zeta phosphorylated on Ser58 and employing native-PAGE and cross-linking techniques, we found that 14-3-3 phosphorylated on Ser58 is monomeric both in vitro and in vivo. Phosphorylated 14-3-3 was detected solely as a monomer, indicating that phosphorylation of a single monomer within a dimer is sufficient to disrupt the dimeric structure. Significantly, phosphorylation-induced monomerization did not prevent 14-3-3 binding to a phosphopeptide target. We propose that this regulated monomerization of 14-3-3 controls its ability to modulate the activity of target proteins and thus may have significant implications for 14-3-3 function and the regulation of many cellular processes. |
| Databáze: | OpenAIRE |
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