| 背景 | Epidermal growth factor receptor (EGFR/ERBB1) is a ~134 kDa protein. Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses. Known ligands include EGF, TGFA/TGF-alpha, AREG, epigen/EPGN, BTC/betacellulin, epiregulin/EREG and HBEGF/heparin-binding EGF. 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. EGFR is the therapeutic target of cetuximab (Erbitux) and panitumumab (Vectibix). 1. Arcaro, A. et al. (2000) Molecular and cellular biology 20, 3817-30. PMID: 108057252. Runkle, KB. et al. (2016) Molecular cell 62, 385-396. PMID: 271535364. Bu, J. et al. (2022) Acta biochimica et biophysica Sinica 54, 400-408. PMID: 355380336. Kochupurakkal, BS. et al. (2005) The Journal of biological chemistry 280, 8503-12. PMID: 156110798. Lu, C. et al. (2010) Molecular and cellular biology 30, 5432-43. PMID: 20837704 |
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