POTENTIAL ROLE OF BCR-ABL IN THE ACTIVATION OF JAK1 KINASE

To study the oncogenic role of the p210(bcr-abl) fusion protein in chr onic myelogenous leukemia cells, we generated a mouse cell line that w as stably transfected with and overexpressed the human p210(bcr-abl) f usion protein, We then looked for phosphorylation activation of the Ja nus-activated kinase (JAK) family of tyrosine-specific protein kinases by the p210(bcr-abl) fusion protein, We found that JAK1, which has be en shown by others to be associated with the IFN-alpha and -gamma plas ma membrane receptors, was phosphorylated to a much greater degree in cells containing the p210(bcr-abl) fusion protein than was the case in the original, untransfected cell line. In contrast, no phosphorylatio n of the JAK2 kinase, which is associated with the IFN-gamma but not I FN-alpha receptor, was observed either with or without p210(bcr-abl) p rotein. A substrate of JAK1, STAT1 (signal transducers and activators of transcription 1), was found to be phosphorylated in cells containin g overexpressed p210(bcr-abl) fusion protein, These results indicate t hat the presence of the p210(bcr-abl) protein kinase within a cell is associated with phosphorylation of the JAK1 kinase and its substrate S TAT1.