Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/9538
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Type: Journal article
Title: The dimeric versus monomeric status of 14-3-3z is controlled by phosphorylation of Ser58 at the dimer interface
Author: Woodcock, J.
Murphy, J.
Stomski, F.
Berndt, M.
Lopez, A.
Citation: Journal of Biological Chemistry, 2003; 278(38):36323-36327
Publisher: Amer Soc Biochemistry Molecular Biology Inc
Issue Date: 2003
ISSN: 0021-9258
1083-351X
Statement of
Responsibility: 
Joanna M. Woodcock, Jane Murphy, Frank C. Stomski, Michael C. Berndt, and Angel F. Lopez
Abstract: 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.
Keywords: NIH 3T3 Cells; Animals; Mice, Inbred BALB C; Rabbits; Mice; Tyrosine 3-Monooxygenase; Serine; 14-3-3 Proteins; Recombinant Proteins; Cross-Linking Reagents; Immunoblotting; Electrophoresis, Polyacrylamide Gel; Signal Transduction; Apoptosis; Amino Acid Motifs; Protein Conformation; Protein Binding; Dimerization; Phosphorylation
RMID: 0020031169
DOI: 10.1074/jbc.M304689200
Appears in Collections:Medicine publications

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