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.
Liu
Y C
YC
Division of Immunobiology, La Jolla Institute for Allergy and Immunology, La Jolla, California 92037, USA.
Elly
C
C
Yoshida
H
H
Bonnefoy-Berard
N
N
Altman
A
A
D048948:14-3-3 Proteins; D001483:Base Sequence; D015153:Blotting, Western; D002460:Cell Line; D002850:Chromatography, Gel; D017931:DNA Primers; D004926:Escherichia coli; D006801:Humans; D007938:Leukemia; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D016296:Mutagenesis; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011485:Protein Binding; D014176:Protein Biosynthesis; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011506:Proteins / Q000302:isolation & purification / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D050721:Proto-Oncogene Proteins c-cbl; D019908:Proto-Oncogene Proteins c-raf; D011519:Proto-Oncogenes; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000378:metabolism; D017384:Sequence Deletion; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014446:Tyrosine 3-Monooxygenase; D044767:Ubiquitin-Protein Ligases
D048948:14-3-3 Proteins; D017931:DNA Primers; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D011506:Proteins; D011518:Proto-Oncogene Proteins; D050721:Proto-Oncogene Proteins c-cbl; D019908:Proto-Oncogene Proteins c-raf; D011993:Recombinant Fusion Proteins; D014446:Tyrosine 3-Monooxygenase; D044767:Ubiquitin-Protein Ligases; C067419:CBL protein, human