Tyrosine phosphorylation of BCR by FPS/FES protein-tyrosine kinases induces association of BCR with GRB-2/SOS.
The human bcr gene encodes a protein with serine/threonine kinase activity, CDC24/dbl homology, a GAP domain, and an SH2-binding region. However, the precise physiological functions of BCR are unknown. Coexpression of BCR with the cytoplasmic protein-tyrosine kinase encoded by the c-fes proto-oncogene in Sf-9 cells resulted in stable BCR-FES protein ... complex formation and tyrosine phosphorylation of BCR. Association involves the SH2 domain of FES and a novel binding domain localized to the first 347 amino acids of the FES N-terminal region. Deletion of the homologous N-terminal BCR-binding domain from v-fps, a fes-related transforming oncogene, abolished transforming activity and tyrosine phosphorylation of BCR in vivo. Tyrosine phosphorylation of BCR in v-fps-transformed cells induced its association with GRB-2/SOS, the RAS guanine nucleotide exchange factor complex. These data provide evidence that BCR couples the cytoplasmic protein-tyrosine kinase and RAS signaling pathways.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Animals, Cell Line, Cell Transformation, Neoplastic, Fusion Proteins, gag-onc, GRB2 Adaptor Protein, Guanine Nucleotide Exchange Factors, Humans, Oncogene Proteins, Oncogenes, Phosphorylation, Phosphotyrosine, Protein Binding, Protein-Tyrosine Kinases, Proteins, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-bcr, Receptor, Epidermal Growth Factor, Recombinant Fusion Proteins, Recombinant Proteins, Restriction Mapping, Sequence Deletion, Spodoptera, Transfection, Tyrosine, ras Guanine Nucleotide Exchange Factors
Adaptor Proteins, Signal Transducing, Animals, Cell Line, Cell Transformation, Neoplastic, Fusion Proteins, gag-onc, GRB2 Adaptor Protein, Guanine Nucleotide Exchange Factors, Humans, Oncogene Proteins, Oncogenes, Phosphorylation, Phosphotyrosine, Protein Binding, Protein-Tyrosine Kinases, Proteins, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-bcr, Receptor, Epidermal Growth Factor, Recombinant Fusion Proteins, Recombinant Proteins, Restriction Mapping, Sequence Deletion, Spodoptera, Transfection, Tyrosine, ras Guanine Nucleotide Exchange Factors
Mol. Cell. Biol.
Date: Feb. 01, 1995
PubMed ID: 7529874
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