Erythropoietin signaling. EPO binding to the homodimeric EpoR on the cell surface changes the conformation of EpoR and brings the respective cytoplasmic domains in closer proximity resulting in transphosphorylation and activation of the associated Janus kinase JAK2 proteins. JAK2 activation results in phosphorylation, dimerization, and translocation of signal transducer and activator of transcription (STAT) proteins, and activation of other downstream signaling pathways such as mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K/AKT), and, in neuronal cells, nuclear factor-(NF-) κB (p50 and p65) with dissociation and degradation of the inhibitory IκB protein.
