title: Differential complementation of Bcr-Abl point mutants with c-Myc.
abstract: A complementation strategy was developed to define the signaling pathways activated by the Bcr-Abl tyrosine kinase. Transformation inactive point mutants of Bcr-Abl were tested for complementation with c-Myc. Single point mutations in the Src-homology 2 (SH2) domain, the major tyrosine autophosphorylation site of the kinase domain, and the Grb-2 binding site in the Bcr region impaired the transformation of fibroblasts by Bcr-Abl. Hyperexpression of c-Myc efficiently restored transformation activity only to the Bcr-Abl SH2 mutant. These data support a model in which Bcr-Abl activates at least two independent pathways for transformation. This strategy may be useful for discerning signaling pathways activated by other oncogenes.
authors.affiliation: Department of Microbiology and Molecular Genetics, University of California-Los Angeles 90024-1489.
authors.forename: D E
authors.initials: DE
authors.lastname: Afar
authors.forename: A
authors.initials: A
authors.lastname: Goga
authors.forename: J
authors.initials: J
authors.lastname: McLaughlin
authors.forename: O N
authors.initials: ON
authors.lastname: Witte
authors.forename: C L
authors.initials: CL
authors.lastname: Sawyers
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D016044:Fusion Proteins, bcr-abl / Q000235:genetics* / Q000502:physiology; D051380:GRB2 Adaptor Protein; D015870:Gene Expression; D016313:Genes, abl; D016259:Genes, myc; D005816:Genetic Complementation Test; D008969:Molecular Sequence Data; D010766:Phosphorylation; D017354:Point Mutation; D011506:Proteins / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000502:physiology; D051381:Rats; D012190:Retroviridae / Q000502:physiology; D015398:Signal Transduction; D014162:Transfection; D014443:Tyrosine / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051380:GRB2 Adaptor Protein; C495950:Grb2 protein, rat; D011506:Proteins; D016271:Proto-Oncogene Proteins c-myc; D014443:Tyrosine; D016044:Fusion Proteins, bcr-abl