BCR-ABL binds to IRS-1 and IRS-1 phosphorylation is inhibited by imatinib in K562 cells.
In the present study we used K562 cells to demonstrate that insulin receptor substrate 1 (IRS-1) is expressed and constitutively phosphorylated in BCR-ABL(+) cells. We observed association between BCR-ABL/IRS-1, IRS-1/phosphoinositide 3'-kinase (PI3-kinase), and IRS-1/Grb2 in the K562 cell line. Our findings demonstrate that imatinib treatment resulted in marked attenuation of BCR-ABL/IRS-1 association and of IRS-1-stimulated PI3-kinase activity in K562 cells. We concluded that the IRS-1 protein is involved in the signalling pathway of the BCR-ABL tyrosine kinase.
Traina
Fabíola
F
Hemocentro, Departamento de Clínica Médica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, P.O. Box 6198, 13083-970 Campinas, SP, Brazil.
Carvalheira
José Barreto C
JB
Saad
Mario J A
MJ
Costa
Fernando F
FF
Saad
Sara T O
ST
D048868:Adaptor Proteins, Signal Transducing; D001549:Benzamides; D015153:Blotting, Western; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016044:Fusion Proteins, bcr-abl / Q000378:metabolism*; D051380:GRB2 Adaptor Protein; D018922:HL-60 Cells; D006801:Humans; D000068877:Imatinib Mesylate; D055504:Insulin Receptor Substrate Proteins; D020014:K562 Cells; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D011506:Proteins / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology*
D048868:Adaptor Proteins, Signal Transducing; D001549:Benzamides; D004791:Enzyme Inhibitors; D051380:GRB2 Adaptor Protein; C495948:GRB2 protein, human; C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins; D010750:Phosphoproteins; D010879:Piperazines; D011506:Proteins; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D019869:Phosphatidylinositol 3-Kinases; D016044:Fusion Proteins, bcr-abl