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Figure 5 | Cell Communication and Signaling

Figure 5

From: Src family kinases interfere with dimerization of STAT5A through a phosphotyrosine-SH2 domain interaction

Figure 5

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.

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