Signaling and transforming properties of BCR-ABL mutants
| BCR-ABL mutant . | Signaling protein binding/ pathways abrogated . | Growth factor independence of hematopoietic cells . | In vitro transformation* . | CML-like disease in mice . |
|---|---|---|---|---|
| P210ΔSH2 | Tyrosine phosphorylated proteins55,56, PI3-kinase/AKT (?)42,53,54 57 | +30 60 | −55 56 | −53 54 |
| P210 Y177F | Grb-2/Sos/Ras31 | +30 31 | −31 | −59 |
| P185Δ176-427 | Grb-2/Sos/Ras31/14-3-336,58/Raf143/ PI3-kinase/AKT42 | +30 | −31 36 | ND |
| P185 TM† (Y177F, R552L, Y793F) | Grb-2/Sos/Ras31 tyrosine phosphorylated proteins55 56 | +/−30 31 ‡ | −31 | ND |
| BCR-ABL mutant . | Signaling protein binding/ pathways abrogated . | Growth factor independence of hematopoietic cells . | In vitro transformation* . | CML-like disease in mice . |
|---|---|---|---|---|
| P210ΔSH2 | Tyrosine phosphorylated proteins55,56, PI3-kinase/AKT (?)42,53,54 57 | +30 60 | −55 56 | −53 54 |
| P210 Y177F | Grb-2/Sos/Ras31 | +30 31 | −31 | −59 |
| P185Δ176-427 | Grb-2/Sos/Ras31/14-3-336,58/Raf143/ PI3-kinase/AKT42 | +30 | −31 36 | ND |
| P185 TM† (Y177F, R552L, Y793F) | Grb-2/Sos/Ras31 tyrosine phosphorylated proteins55 56 | +/−30 31 ‡ | −31 | ND |
In vitro transformation by individual mutants assessed by suppression of contact-dependent growth in a Rat-1 focus formation assay, abrogation of anchorage-dependent growth in a Rat-1 soft agar colony formation assay, or propagation of lymphoid cells in long-term bone marrow cultures.
P185 triple mutant (P185 TM) contains a mutation in the Grb-2 binding site (Y177F), the phosphotyrosine-binding site within the SH2 domain (R552L), and an autophosphorylation site (Y793F).
P185 TM confers IL-3 independence to BaF3 but not to 32D cells.30 ND indicates not determined.