Abstract
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.
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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Adaptor Proteins, Signal Transducing*
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Animals
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Cell Line
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Cell Transformation, Neoplastic
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ErbB Receptors / metabolism*
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Fusion Proteins, gag-onc / metabolism*
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GRB2 Adaptor Protein
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Guanine Nucleotide Exchange Factors
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Humans
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Oncogene Proteins / biosynthesis
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Oncogene Proteins / isolation & purification
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Oncogene Proteins / metabolism*
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Oncogenes
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Phosphorylation
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Phosphotyrosine
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Protein Binding
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Protein-Tyrosine Kinases / biosynthesis
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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 Mas
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Proto-Oncogene Proteins c-bcr
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Proto-Oncogene Proteins*
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Recombinant Fusion Proteins
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Recombinant Proteins / biosynthesis
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Recombinant Proteins / metabolism
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Restriction Mapping
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Sequence Deletion
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Spodoptera
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Transfection
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Tyrosine / analogs & derivatives
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Tyrosine / metabolism
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ras Guanine Nucleotide Exchange Factors
Substances
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Adaptor Proteins, Signal Transducing
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Fusion Proteins, gag-onc
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GRB2 Adaptor Protein
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GRB2 protein, human
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Guanine Nucleotide Exchange Factors
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MAS1 protein, human
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Oncogene Proteins
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Proteins
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Proto-Oncogene Mas
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Proto-Oncogene Proteins
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Recombinant Fusion Proteins
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Recombinant Proteins
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ras Guanine Nucleotide Exchange Factors
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Phosphotyrosine
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Tyrosine
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ErbB Receptors
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Protein-Tyrosine Kinases
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v-fps oncogene protein, Fujinami sarcoma virus
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BCR protein, human
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Proto-Oncogene Proteins c-bcr