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. 2022 Feb 25;15:1349–1364. doi: 10.2147/JIR.S353489

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© 2022 Mengie Ayele et al.

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Schematic representation of the JAK2/STAT3 signaling pathway. (1) Receptor binding: Ligands such as cytokines and growth factors bind to extracellular domains of the receptors. (2) JAK2 phosphorylation: Following ligand binding receptor-associated JAK2 undergo phosphorylation to each other. (3) STAT3 phosphorylation: Activated JAK2 kinase domain (JH1) phosphorylates cytoplasmic tails of receptors, recruiting STAT3 to the receptor, and becomes phosphorylated at Tyr 705. (4) Dimerization: Phosphorylated STAT3 dimerizes at SH2 domain. (5) Translocation: Dimerized STAT3 translocates into the nucleus where it binds to the promoter region of DNA. (6) Gene Expression: Dimerized STAT3 acts as transcription factor and activates the transcription of target genes involved in regulating cell growth.