Identification of Flt3 internal tandem duplications downstream targets by high-throughput immunoblotting protein array system.
The receptor tyrosine kinase Flt3 plays an important role in proliferation and survival of hematopoietic cells. Flt3 is the most frequently mutated gene (20-30%) in cases of acutemyeloid leukemia (AML). The majority of Flt3 mutations are internal tandem duplications (ITD) in the juxtamembrane domain of Flt3 receptor. This mutation results in the constitutive activation of STAT5 and Ras/mitogen-activated protein kinase pathways, leading to the aberrant growth of AML cells. In this study, to better understand the mechanisms of Flt3-ITD to the downstream pathways, a high-throughput immunoblotting protein array system was employed. As a result, c-Jun and c-Raf were markedly induced, suggesting that these factors are functional downstream targets of Flt3-ITD.
Takahashi
Shinichiro
S
Department of Infection Control and Laboratory Diagnostics, Tohoku University Graduate School of Medicine, Sendai, Japan. shintak@mail.tains.tohoku.ac.jp
D000818:Animals; D045744:Cell Line, Tumor; D015870:Gene Expression; D016758:Genes, jun / Q000235:genetics*; D015151:Immunoblotting; D051379:Mice; D009154:Mutation; D040081:Protein Array Analysis / Q000379:methods*; D019908:Proto-Oncogene Proteins c-raf / Q000235:genetics*; D020080:Tandem Repeat Sequences / Q000235:genetics*; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
C497971:Flt3 protein, mouse; D051941:fms-Like Tyrosine Kinase 3; D019908:Proto-Oncogene Proteins c-raf