Figure 2. Canonical Jak2-Stat5a/b signaling in prostate cancer cells and functional interaction with AR signaling.

Various levels of inhibition are possible in the Stat5a/b signaling cascade to block Stat5a/b target gene expression, including targeting of cytokine receptor activation, Jak2 kinase-mediated phosphorylation, and Stat5a/b dimerization, DNA binding and transcriptional activity. Physical interaction between Stat5a/b and AR has been reported, providing a mechanistic basis for crosstalk between these two pathways, which results in reciprocal synergistic effects on nuclear localization and transcriptional activity. Depicted are known Stat5a/b target genes Bcl-xL and cyclin D1 and AR target gene PSA. Abbreviations: AR, androgen receptor; ARE, androgen response element; CYT, cytokine; CYTR, cytokine receptor; DHT, dihydrotestosterone; GAS, gamma-interferon activation sequence; GF, growth factor; HSP, heat shock protein; pY, phosphotyrosine.