Deletion of the ABL SH3 domain reactivates de-oligomerized BCR-ABL for growth factor independence.
Biological activities of BCR-ABL, an activated tyrosine kinase oncogene responsible for pathogenesis of human leukemias, can be completely inactivated by a deletion of the BCR aminoterminal sequence with tetramerizing property (BCR-ABL delta 1-40). We attempted several ways to restore the ability to induce growth factor independence to the de-oligomerized BCR-ABL delta 1-40 and found that an additional deletion of the ABL SH3 domain could. In BCR-ABL delta 1-40 reactivated by the SH3 deletion, transphosphoryation of other cellular proteins like p62 or SHC in vivo and autophosphorylation with recruitment of GRB-2 were also recovered.
Maru
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Y
Department of Genetics, Institute of Medical Science, University of Tokyo, Japan.
Witte
O N
ON
Shibuya
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D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002460:Cell Line; D016044:Fusion Proteins, bcr-abl / Q000235:genetics* / Q000378:metabolism*; D051380:GRB2 Adaptor Protein; D016259:Genes, myc; D007377:Interleukin-3 / Q000378:metabolism; D051379:Mice; D010766:Phosphorylation; D011506:Proteins / Q000235:genetics* / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion; D014443:Tyrosine / Q000378:metabolism; D018909:src Homology Domains
D048868:Adaptor Proteins, Signal Transducing; D051380:GRB2 Adaptor Protein; C495949:Grb2 protein, mouse; D007377:Interleukin-3; D011506:Proteins; D016271:Proto-Oncogene Proteins c-myc; D014443:Tyrosine; D016044:Fusion Proteins, bcr-abl