查看文章

The BCR-ABL oncogene encodes an activated fusion tyrosine kinase that causes chronic myelogenous leukemia (CML) and B-lymphoid acute lymphoblastic leukemia (B-ALL) in humans. An autophosphorylation site at Tyr 177 of BCR-ABL recruits Grb2 via its SH2 domain, and is required for efficient induction of CML-like myeloproliferative disease by BCR-ABL in a mouse BM retroviral transduction/transplantation model. We showed previously (Sattler et al., Cancer Cell2002;1:479) that the scaffolding/adapter protein Gab2 is recruited to Y177 of BCR-ABL via a Grb2/Gab2 complex, and in vitro transformation of primary myeloid and lymphoid progenitors by BCR-ABL was impaired in bone marrow from mice with homozygous null mutations in the Gab2 gene (Gab2^−/− mice), coincident with decreased activation of the ERK and Akt signaling pathways. Here, we demonstrate an essential requirement for Gab2 in …