Figure 5From: Src family kinases interfere with dimerization of STAT5A through a phosphotyrosine-SH2 domain interaction Activated SFK interfere with dimerization and nuclear translocation of pSTAT5A in BCR-ABL expressing cells. Left scheme: Classical activation of the JAK2-STAT5A signaling pathway downstream of the EpoR. Right scheme: BCR-ABL directly phosphorylates STAT5AY694 resulting in STAT5A dimerization, nuclear accumulation and finally target gene expression [10]. In the presence of BCR-ABL, a predominantly cytoplasmic localization of pSTAT5A is achieved (i) upon binding to the scaffolding adaptor Gab2 resulting in pro-survival signaling through PI3K/Akt activation [35] and (ii) through binding of the STAT5A SH2 domain to the phosphorylated activation loop of SFK, a mechanism that interferes with STAT5A dimerization and subsequent nuclear accumulation. Constitutively active STAT5AS710F escapes the SFK-mediated cytoplasmic retention. Flashes indicate phosphorylation events.Back to article page