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Beschreibung

Epidermal growth factor receptor (UniProt: P00533, also known as EC: 2.7.10.1, Proto-oncogene c-ErbB1, Receptor tyrosine protein kinase erbB-1) is encoded by the EGFR (also known as ERBB, ERBB1, HER1) gene (Gene ID: 1956) in human. EGFR is activated by binding of its specific ligands and transforms from a monomeric to active homodimeric form. In addition to forming homodimers, EGFR may pair with another member of the ErbB receptor family, such as ErbB2/Her2/neu, to create an activated heterodimer. EGFR dimerization stimulates its intrinsic intracellular protein-tyrosine kinase activity. As a result, autophosphorylation of five tyrosine residues (Y992, Y1045, Y1068, Y1148 and Y1173) occurs in the C-terminal domain. This autophosphorylation elicits downstream activation and signaling by several other proteins that associate with the phosphorylated tyrosines through their own phosphotyrosine-binding domains. EGFR activation results in at least 4 major downstream signaling cascades including the RAS-RAF-MEK-ERK, PI3 kinase-AKT, PLC gamma-PKC and STATs modules. These downstream events modulate several cell functions, including migration, adhesion, and proliferation. Endocytosis and inhibition of the activated EGFR by phosphatases constitute key regulatory mechanisms.