Human Epidermal Growth Factor Receptor, EGFR ELI

Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed: 2790960, PubMed: 10805725, PubMed: 27153536).

Known ligands include EGF, TGFA/TGF-alpha, AREG, epigen/EPGN, BTC/betacellulin, epiregulin/EREG and HBEGF/heparin-binding EGF (PubMed: 2790960, PubMed: 7679104, PubMed: 8144591, PubMed: 9419975, PubMed: 15611079, PubMed: 12297049, PubMed: 27153536, PubMed: 20837704, PubMed: 17909029).

Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation on key cytoplasmic residues.

The phosphorylated receptor recruits adapter proteins like GRB2 which in turn activates complex downstream signaling cascades.

Activates at least 4 major downstream signaling cascades including the RAS-RAF-MEK-ERK, PI3 kinase-AKT, PLCgamma-PKC and STATs modules (PubMed: 27153536).

May also activate the NF-kappa-B signaling cascade (PubMed: 11116146).

Also directly phosphorylates other proteins like RGS16, activating its GTPase activity and probably coupling the EGF receptor signaling to the G protein-coupled receptor signaling (PubMed: 11602604).

Also phosphorylates MUC1 and increases its interaction with SRC and CTNNB1/beta-catenin (PubMed: 11483589).

Positively regulates cell migration via interaction with CCDC88A/GIV which retains EGFR at the cell membrane following ligand stimulation, promoting EGFR signaling which triggers cell migration (PubMed: 20462955).

Plays a role in enhancing learning and memory performance (By similarity).

Isoform 2 may act as an antagonist of EGF action.

(Microbial infection) Acts as a receptor for hepatitis C virus (HCV) in hepatocytes and facilitates its cell entry.

Mediates HCV entry by promoting the formation of the CD81-CLDN1 receptor complexes that are essential for HCV entry and by enhancing membrane fusion of cells expressing HCV envelope glycoproteins.