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. 2020 Sep 18;9:F1000 Faculty Rev-1153. [Version 1] doi: 10.12688/f1000research.26648.1

Figure 3. Activation of erythropoietin receptor (EPOR) by EPO.

Figure 3.

A single EPO molecule binds and stabilizes EPOR–JAK2 complex dimers, inducing a conformational change that initiates JAK2 trans-phosphorylation and activation. Active JAK2 phosphorylates multiple tyrosine residues on STAT5 and the cytoplasmic domain of EPOR, triggering a signaling cascade that activates numerous effector pathways contributing to biological activity. Dashed lines represent kinase activity. For simplicity, the kinase activity of only one JAK2 protein is indicated. Major signaling pathways activated by EPOR include Ras/MAPK, STAT5, and PI3K/Akt, which drive the expression of genes that promote erythroid progenitor survival, proliferation, and differentiation as well as feedback inhibition of EPOR signaling. MAPK, mitogen-activated protein kinase; PI3K, phosphoinositide-3 kinase; STAT5, signal transducer and activator of transcription 5.