Signaling pathways and proteins that increase or decrease STAT5 signaling in normal mammary epithelial cells. Research to date has identified several factors that contribute to higher levels of STAT5 activation or, conversely, reduce activation levels in normal mammary epithelial cells. E74-like factor 5 (ets domain transcription factor) (ELF5) acts in the PRL/JAK2 signaling pathway to increase levels of STAT5 activation in normal mammary epithelial cells. Other signaling pathway components that increase STAT5 activation are EGF, ErbB2, transforming growth factor-alpha (TGF-α), estrogen acting with the progesterone pathway acting downstream, GH/JAK2, IGF, and c-Src. The TGF-β signaling pathway can decrease STAT5 activation levels. Cellular proteins that contribute to increased STAT5 activation include PI 3-kinase enhancer A (PIKE-A), serine/threonine protein kinase Akt 1 (AKT-1), p21-activated kinase 1 (Pak1), the phosphotyrosine phosphatase Shp2, beta-integrin, and dystroglycan. Cellular proteins that have been shown to decrease STAT5 activation levels include caveolin-1 and suppressor of cytokine signaling 3 (SOCS-3). c-Src, human cellular-Src; EGF, epidermal growth factor; ErbB4, v-erb-b2 erythroblastic leukemia viral oncogene homolog 4, neuro/glioblastoma-derived oncogene homolog (avian); GH, growth hormone; IGF, insulin growth factor; JAK2, Janus kinase 2; PRL, prolactin; Shp2, Src homology region 2 domain-containing phosphatase-2; STAT5, signal transducer and activator of transcription 5.
