Characterization of the transforming activity of p80, a hyperphosphorylated protein in a Ki-1 lymphoma cell line with chromosomal translocation t(2;5).

摘要: Abstract We have molecularly cloned a cDNA encoding protein uniquely expressed and hyperphosphorylated at tyrosine residues in Ki-1 lymphoma cell that contained chromosomal translocation t(2;5). The encoded p80 was shown to be generated by fusion of protein-tyrosine kinase nucleolar B23/nucleophosmin (NPM). coding sequence this turned out virtually identical the for NPM-anaplastic (ALK) previously from transcript gene breakpoint same translocation. Overexpression NIH 3T3 cells induced neoplastic transformation, suggesting is aberrantly activated. normal form predicted receptor-type on basis its similarity insulin receptor family kinases. However, an immunofluorescence study using COS revealed localized cytoplasm. Thus, subcellular activation presumably structural alteration would cause malignant transformation. We also showed mutant lacking NPM portion unable transform cells. essential transforming activity, responsible oncogenesis. Finally, Shc substrate 1 (IRS-1) were tyrosine-phosphorylated bound p80-transformed mutants defective binding phosphorylation could Association these with GRB2 still observed, interaction but not or IRS-1 relevant