Potential role of bcr-abl in the activation of JAK1 kinase.
To study the oncogenic role of the p210(bcr-abl) fusion protein in chronic myelogenous leukemia cells, we generated a mouse cell line that was stably transfected with and overexpressed the human p210(bcr-abl) fusion protein. We then looked for phosphorylation activation of the Janus-activated kinase (JAK) family of tyrosine-specific protein kinases by the p210(bcr-abl) fusion protein. We found that JAK1, which has been shown by others to be associated with the IFN-alpha and -gamma plasma 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 phosphorylation of the JAK2 kinase, which is associated with the IFN-gamma but not IFN-alpha receptor, was observed either with or without p210(bcr-abl) protein. A substrate of JAK1, STAT1 (signal transducers and activators of transcription 1), was found to be phosphorylated in cells containing overexpressed p210(bcr-abl) fusion protein. These results indicate that the presence of the p210(bcr-abl) protein kinase within a cell is associated with phosphorylation of the JAK1 kinase and its substrate STAT1.
Henderson
Y C
YC
Department of Hematology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Guo
X Y
XY
Greenberger
J
J
Deisseroth
A B
AB
D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism; D004789:Enzyme Activation; D016044:Fusion Proteins, bcr-abl / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D053613:Janus Kinase 1; D020014:K562 Cells; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D050794:STAT1 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism; D014162:Transfection
D004268:DNA-Binding Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D015534:Trans-Activators; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl; C507904:JAK1 protein, human; C507905:Jak1 protein, mouse; D053613:Janus Kinase 1