Fig. 8

A model of EGFR-mediated KDELR endocytosis and STAT3 signaling activation induced by KDEL ligand. Secreted ER proteins bind to surface-localized KDELR and induce oligomerization of the receptor, leading to KDELR-interacting EGFR monomers in close proximity for tyrosine phosphorylation. Phosphorylated EGFR initiates clathrin-mediated internalization of KDELR and EGFR, resulting in transport of these two receptors to the Golgi apparatus and back to the cell surface. STAT3 activated by phosphorylated EGFR transmits signals to the nucleus and induces transcription of genes that control cell proliferation and migration