Receptor Tyrosine Kinase-EGFR

EGFR, also known as ERBB1 and HER1, is a transmembrane tyrosine kinase receptor (RTK). EGFR is a member of the human epidermal receptor (HER) family and a crucial component of cell signal pathways. Binding with ligands (EGF and TGF-α) leads to conformational changes in EGFR homo-dimerization or hetero-dimerization with other HER family members HER2, HER3 and ERBB4. Overexpression and activating mutations of EGFR, which have been reported in up to 30% of solid tumors (including breast, colorectal, lung, pancreatic, gastric, head and neck cancer, and glioblastomas.). Among more than one hundred proteins found to interact with EGFR, growth factor receptorbound protein 2 (GRB2) which binds to phosphorylated tyrosines 1068, 1086, and 1148. RAS is subsequently activated by phosphorylation, a modification that relies on son of sevenless (SOS). Activated RAS binds to RAF, and this interaction leads to mitogen-activated protein kinase kinase 1 (MEK1) followed by extracellular signalregulated kinases 1/2 (ERK1/2) phosphorylations. EGFR phosphorylation the activation of PI3K that subsequently promotes AKT activation. In some tumor cells c-Met communicates through the Ras/MAPK signaling pathway with EGFR, which results in HGF-independent activation of c-Met signaling.

References:

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