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 ras-GAP associated protein.
Original language | English (US) |
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Pages (from-to) | 295-301 |
Number of pages | 7 |
Journal | Leukemia |
Volume | 9 |
Issue number | 2 |
State | Published - Feb 1995 |
Keywords
- BCR-ABL
- CML
- Philadelphia chromosome
ASJC Scopus subject areas
- Hematology
- Oncology
- Cancer Research