Tyrosine protein kinase substrates in Philadelphia-positive human chronic granulocytic leukemia derived cell lines (K562 and BV173): detection by using an immunoblotting technique.
In chronic granulocytic leukemia (CGL) the Philadelphia translocation results in the production of a novel 210 kDa bcr-abl fusion protein which shows increased tyrosine protein kinase activity in comparison with its normal 145 kDa c-abl counterpart. Using an immunoblotting method and antiphosphotyrosine antibody, we have identified the tyrosine protein kinase substrates present in intact cells from two Philadelphia-positive CGL derived cell lines (K562 and BV173) and compared these with the substrates present in a Philadelphia-negative myeloid cell line (HL60). We have demonstrated an increased number of substrates, particularly of low (less than 110 kDa) molecular weight in the K562 or BV173 cells compared with the HL60 cells. There is virtual identity of the substrates present in the two CGL-derived lines. This work supports the hypothesis that the functional changes present in the bcr-abl 210 kDa protein of CGL results in altered tyrosine phosphorylation of intracellular proteins and that this is of importance in the pathogenesis of CGL.
D006801:Humans; D007163:Immunosorbent Techniques; D007951:Leukemia, Myeloid / Q000378:metabolism*; D008970:Molecular Weight; D009363:Neoplasm Proteins / Q000378:metabolism*; D010677:Philadelphia Chromosome; D010750:Phosphoproteins / Q000378:metabolism*; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D009363:Neoplasm Proteins; D010750:Phosphoproteins; D019000:Phosphotyrosine; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases