Activation-modulated association of 14-3-3 proteins with Cbl in T cells.
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.
Mesh Terms:
1-Phosphatidylinositol 3-Kinase, 14-3-3 Proteins, Base Sequence, Blotting, Western, Cell Line, Chromatography, Gel, DNA Primers, Escherichia coli, Humans, Leukemia, Lymphocyte Activation, Molecular Sequence Data, Mutagenesis, Phosphotransferases (Alcohol Group Acceptor), Polymerase Chain Reaction, Protein Binding, Protein Biosynthesis, Protein-Serine-Threonine Kinases, Protein-Tyrosine Kinases, Proteins, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-cbl, Proto-Oncogene Proteins c-raf, Proto-Oncogenes, Recombinant Fusion Proteins, Sequence Deletion, Signal Transduction, T-Lymphocytes, Tumor Cells, Cultured, Tyrosine 3-Monooxygenase, Ubiquitin-Protein Ligases
1-Phosphatidylinositol 3-Kinase, 14-3-3 Proteins, Base Sequence, Blotting, Western, Cell Line, Chromatography, Gel, DNA Primers, Escherichia coli, Humans, Leukemia, Lymphocyte Activation, Molecular Sequence Data, Mutagenesis, Phosphotransferases (Alcohol Group Acceptor), Polymerase Chain Reaction, Protein Binding, Protein Biosynthesis, Protein-Serine-Threonine Kinases, Protein-Tyrosine Kinases, Proteins, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-cbl, Proto-Oncogene Proteins c-raf, Proto-Oncogenes, Recombinant Fusion Proteins, Sequence Deletion, Signal Transduction, T-Lymphocytes, Tumor Cells, Cultured, Tyrosine 3-Monooxygenase, Ubiquitin-Protein Ligases
J. Biol. Chem.
Date: Jun. 14, 1996
PubMed ID: 8663231
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