Abstract
14-3-3 proteins have recently been implicated in the regulation of intracellular signaling pathways via their interaction with several oncogene and protooncogene products. We found recently that 14-3-3 associates with several tyrosine-phosphorylated proteins and phosphatidylinositol 3-kinase (PI3-K) in T cells. We report here the identification of the 120-kDa 14-3-3tau-binding phosphoprotein present in activated T cell lysates as Cbl, a protooncogene product of unknown function which was found recently to be a major protein-tyrosine kinase (PTK) substrate, and to interact with several signaling molecules including PI3-K, in T lymphocytes. The association between 14-3-3tau and Cbl was detected both in vitro and in intact T cells and, in contrast to Raf-1, was markedly increased following T cell activation. The use of truncated 14-3-3tau fusion proteins demonstrated that the 15 C-terminal residues are required for the association between 14-3-3 and three of its target proteins, namely, Cbl, Raf-1, and PI3-K. The findings that 14-3-3tau binds both PI3-K and Cbl, together with recent reports of an association between Cbl and PI3-K, suggest that 14-3-3 dimers play a critical role in signal transduction processes by promoting and coordinating protein-protein interactions of signaling proteins.
Publication types
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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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Base Sequence
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Blotting, Western
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Cell Line
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Chromatography, Gel
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DNA Primers
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Escherichia coli
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Humans
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Leukemia
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Lymphocyte Activation*
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Molecular Sequence Data
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Mutagenesis
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Phosphatidylinositol 3-Kinases
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Phosphotransferases (Alcohol Group Acceptor) / antagonists & inhibitors
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Phosphotransferases (Alcohol Group Acceptor) / metabolism
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Polymerase Chain Reaction
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Protein Binding
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Protein Biosynthesis
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Protein Serine-Threonine Kinases / metabolism
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Protein-Tyrosine Kinases / metabolism
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Proteins / isolation & purification
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Proteins / metabolism*
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Proto-Oncogene Proteins / biosynthesis
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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-cbl
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Proto-Oncogene Proteins c-raf
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Proto-Oncogenes
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Recombinant Fusion Proteins / biosynthesis
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Recombinant Fusion Proteins / metabolism
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Sequence Deletion
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Signal Transduction
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T-Lymphocytes / metabolism*
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Tumor Cells, Cultured
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Tyrosine 3-Monooxygenase*
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Ubiquitin-Protein Ligases*
Substances
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14-3-3 Proteins
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DNA Primers
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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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Proto-Oncogene Proteins c-cbl
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Ubiquitin-Protein Ligases
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Phosphotransferases (Alcohol Group Acceptor)
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Protein-Tyrosine Kinases
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-raf
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CBL protein, human