title: The SH2 domain of ABL is not required for factor-independent growth induced by BCR-ABL in a murine myeloid cell line.
abstract: Chronic myelogenous leukemia (CML) is characterized by the presence of a specific chromosomal translocation between the long arms of chromosomes 9 and 22 that results in the fusion of BCR encoded sequences upstream of exon 2 of c-ABL. This fusion gene produces a 210-kDa chimeric BCR-ABL protein that has elevated tyrosine kinase activity. Several substrates of this activated tyrosine kinase have been reported. However, their necessity for the transforming functions of BCR-ABL has not been determined. A specific deletion of the SH2 domain of ABL was created to determine whether this mutation would alter the ability of BCR-ABL to induce factor-independent growth of a murine myeloid cell line and to determine whether the SH2 domain mediates the interaction of BCR-ABL with any of its substates. Our results indicate that the SH2 domain of BCR-ABL is not required for the induction of growth factor independence and is not required for the association of BCR-ABL with rasGAP or SHC. However, myeloid cells expressing this mutant lack the tyrosine phosphorylation of a 62-kDa rasGAP associated protein.
authors.affiliation: Division of Hematology and Medical Oncology, Oregon Health Sciences University, Portland 97201.
authors.forename: T
authors.initials: T
authors.lastname: Oda
authors.forename: S
authors.initials: S
authors.lastname: Tamura
authors.forename: T
authors.initials: T
authors.lastname: Matsuguchi
authors.forename: J D
authors.initials: JD
authors.lastname: Griffin
authors.forename: B J
authors.initials: BJ
authors.lastname: Druker
mesh_terms: D000818:Animals; D001483:Base Sequence; D016044:Fusion Proteins, bcr-abl / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D020690:GTPase-Activating Proteins; D016313:Genes, abl; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000473:pathology*; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000378:metabolism; D017384:Sequence Deletion; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D020690:GTPase-Activating Proteins; D011506:Proteins; D016044:Fusion Proteins, bcr-abl