Tyrosine phosphorylation of rasGAP and associated proteins in chronic myelogenous leukemia cell lines

The Philadelphia chromosome (Ph¹), detected in virtually all cases of chronic myelogenous leukemia, is formed by a reciprocal translocation between chromosomes 9 and 22 that fuses BCR encoded sequences upstream of exon 2 of c-ABL. This oncogene produces a fusion protein (p210^BCR/ABL) in which the ABL tyrosine kinase activity is elevated. This elevated kinase activity is essential for transformation, but the mechanisms involved are unknown. We report here that p21^ras GTPase activating protein (rasGAP) or rasGAP-associated proteins p190 and p62 are phosphorated on tyrosine in Ph¹ (+) cell lines. Further, rasGAP coimmunoprecipitates with p210^BCR/ABL in these cell lines. These results suggest that rasGAP or associated proteins are potential substrates for p210^BCR/ABL kinase and thus directly link p210^BCR/ABL With a signal transduction pathway known to be activated by hematopoietic growth factors (p21^ras).