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. 2019 Feb 21;9:48. doi: 10.3389/fonc.2019.00048

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Copyright © 2019 Loh, Arya, Naema, Wong, Sethi and Looi.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Activated STAT3/5 signaling pathway by IL-6 receptor, Prolactin (PRL) receptor, VEGF Receptor, EGF Receptor, and IL-10 receptor. STAT3 and STAT5 are activated through tyrosine phosphorylation, then the STAT3/5 moomer undergoes dimerization and translocated into the nucleus. In the nucleus, STAT3/5 dimers binds to the promoter region or γ-interferon activation sequence (GAS) of target genes with co-factors, such as Nuclear Factor Kappa (NF-κB), Hypoxia-inducible factor 1-alpha (HIF-1α), protein kinase B (Akt), and p300 to transcript genes related to inflammation, proliferation, migration, and survival. NF-κB is activated through the phosphorylation of Inhibitor of kappa (IκB-α). PRLR activate Mitogen-activated protein kinase (MAPK) and Phosphoinosite 3-kinase (PI3K) pathways to produce co-regulators that are required for expression of certain STAT5-related genes.