Abstract
The highly conserved and ubiquitously expressed 14-3-3 family of proteins bind to a variety of proteins involved in signal transduction and cell cycle regulation. The nature and specificity of 14-3-3 binding is, however, not known. Here we show that 14-3-3 is a specific phosphoserine-binding protein. Using a panel of phosphorylated peptides based on Raf-1, we have defined the 14-3-3 binding motif and show that most of the known 14-3-3 binding proteins contain the motif. Peptides containing the motif could disrupt 14-3-3 complexes and inhibit maturation of Xenopus laevis oocytes. These results suggest that the interactions of 14-3-3 with signaling proteins are critical for the activation of signaling proteins. Our findings also suggest novel roles for serine/threonine phosphorylation in the assembly of protein-protein complexes.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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14-3-3 Proteins
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3T3 Cells / metabolism
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Amino Acid Sequence
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Animals
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Enzyme Inhibitors / metabolism*
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Female
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Hybridomas
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Isomerism
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Mice
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Molecular Sequence Data
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Oocytes / metabolism
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Phosphopeptides / metabolism
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Phosphorylation
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Phosphoserine / metabolism*
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Protein Binding / physiology
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Protein Serine-Threonine Kinases / metabolism
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Proteins / metabolism*
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-raf
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Sensitivity and Specificity
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Signal Transduction / physiology*
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T-Lymphocytes / metabolism
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Tyrosine 3-Monooxygenase*
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Xenopus
Substances
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14-3-3 Proteins
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Enzyme Inhibitors
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Phosphopeptides
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Proteins
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Proto-Oncogene Proteins
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Phosphoserine
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Tyrosine 3-Monooxygenase
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-raf