Chronic myeloid leukemia is characterized by the Philadelphia (Ph1) translocation t(9;22) that generates a hybrid gene, bcr/abl, translated to a Mr210,000 tyrosine kinase (p210bcr/abl) with transforming activity for hematopoietic cells. Hematopoietic cell transformation by p210bcr/abl seems to involve activation of the Ras signaling pathway by at least two different signaling intermediates, growth factor receptor-bound protein 2 and Src homology and collagen protein, but additional signaling proteins are likely to be required as well. In an effort to identify additional phosphoproteins activated by p210bcr/abl, we studied the murine, interleukin 3-dependent, myeloid cell line, 32D, and a bcr/abl-transfected, factor-independent subline, 32Dp210. The analysis of whole-cell lysates of 32D and 32Dp210 cells showed that several proteins with a molecular weight of Mr50,000–60,000 were phosphorylated on tyrosine residues in 32Dp210 cells. Because Src family kinases have an apparent molecular weight of Mr50,000–60,000, we asked whether they could become activated by p210bcr/abl. Two Src family kinases, p53/56lyn and p59hck, showed a severalfold higher phosphokinase activity in 32Dp210 cells than in 32D cells. Coimmunoprecipitation experiments with anti-Lyn, anti-Hck, and anti-Abl antibodies demonstrated an intracellular association of p210bcr/abl with p53/56lyn and p59hck. Moreover, the phosphokinase activity of p53/56lyn was higher in bcr/abl-positive myeloid cell lines (K562, BV173, and LAMA84) than in the bcr/abl-negative myeloid cell line JOSK-M. In conclusion, the results show that p210bcr/abl induces the activation of at least two Src family kinases, p53/56lyn and p59khck, in myeloid cells. These findings extend the range of potential targets of p210bcr/abl that might mediate its transforming effects.


Supported by the Deutsche Forschungsgemeinschaft, Grants Ha 1680/2-1 and Ha 1680/2-2.

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