Abstract
The cdc25 phosphatases play key roles in cell cycle progression by activating cyclin-dependent kinases. Two members of the 14-3-3 protein family have been isolated in a yeast two-hybrid screen designed to identify proteins that interact with the human cdc25A and cdc25B phosphatases. Genes encoding the human homolog of the 14-3-3 epsilon protein and the previously described 14-3-3 beta protein have been isolated in this screening. 14-3-3 proteins constitute a family of well-conserved eukaryotic proteins that were originally isolated in mammalian brain preparations and that possess diverse biochemical activities related to signal transduction. We present evidence that indicates that cdc25 and 14-3-3 proteins physically interact both in vitro and in vivo. 14-3-3 protein does not, however, affect the phosphatase activity of cdc25A. Raf-1, which is known to bind 14-3-3 proteins, has recently been shown to associate with cdc25A and to stimulate its phosphatase activity. 14-3-3 protein, however, has no effect on the cdc25A-kinase activity of Raf-1. Instead, 14-3-3 may facilitate the association of cdc25 with Raf-1 in vivo, participating in the linkage between mitogenic signaling and the cell cycle machinery.
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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Amino Acid Sequence
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Animals
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Base Sequence
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Cell Cycle Proteins / isolation & purification
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Cell Cycle Proteins / metabolism*
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Cell Line
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Cloning, Molecular
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DNA, Complementary
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HeLa Cells
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Humans
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Molecular Sequence Data
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Phospholipases A / metabolism
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Phosphoprotein Phosphatases / isolation & purification
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Phosphoprotein Phosphatases / metabolism*
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Protein Biosynthesis
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Protein Serine-Threonine Kinases / isolation & purification
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Protein Serine-Threonine Kinases / metabolism
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Proteins / isolation & purification
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Proteins / metabolism*
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Proto-Oncogene Proteins / isolation & purification
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-raf
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Recombinant Fusion Proteins / biosynthesis
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Recombinant Fusion Proteins / isolation & purification
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Recombinant Fusion Proteins / metabolism
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Saccharomyces cerevisiae / metabolism
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Signal Transduction
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Spodoptera
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Transfection
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Tyrosine 3-Monooxygenase*
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cdc25 Phosphatases
Substances
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14-3-3 Proteins
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Cell Cycle Proteins
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DNA, Complementary
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Proteins
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Proto-Oncogene Proteins
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Recombinant Fusion Proteins
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Tyrosine 3-Monooxygenase
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-raf
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Phospholipases A
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Phosphoprotein Phosphatases
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cdc25 Phosphatases