title: Tyrosine phosphorylation of BCR by FPS/FES protein-tyrosine kinases induces association of BCR with GRB-2/SOS.
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.
authors.affiliation: Department of Genetics, University of Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Maru
authors.forename: K L
authors.initials: KL
authors.lastname: Peters
authors.forename: D E
authors.initials: DE
authors.lastname: Afar
authors.forename: M
authors.initials: M
authors.lastname: Shibuya
authors.forename: O N
authors.initials: ON
authors.lastname: Witte
authors.forename: T E
authors.initials: TE
authors.lastname: Smithgall
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D066246:ErbB Receptors / Q000378:metabolism*; D015681:Fusion Proteins, gag-onc / Q000378:metabolism*; D051380:GRB2 Adaptor Protein; D020662:Guanine Nucleotide Exchange Factors; D006801:Humans; D015513:Oncogene Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D009857:Oncogenes; D010766:Phosphorylation; D019000:Phosphotyrosine; D011485:Protein Binding; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000378:metabolism*; D011506:Proteins / Q000302:isolation & purification / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D051562:Proto-Oncogene Proteins c-bcr; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D015183:Restriction Mapping; D017384:Sequence Deletion; D018411:Spodoptera; D014162:Transfection; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D020663:ras Guanine Nucleotide Exchange Factors
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015681:Fusion Proteins, gag-onc; D051380:GRB2 Adaptor Protein; C495948:GRB2 protein, human; D020662:Guanine Nucleotide Exchange Factors; C000715470:MAS1 protein, human; D015513:Oncogene Proteins; D011506:Proteins; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D020663:ras Guanine Nucleotide Exchange Factors; D019000:Phosphotyrosine; D014443:Tyrosine; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; C068415:v-fps oncogene protein, Fujinami sarcoma virus; C496613:BCR protein, human; D051562:Proto-Oncogene Proteins c-bcr