EGF Signaling

The epidermal growth factor (EGF) family is a group of structurally related proteins that regulate cell proliferation, migration and differentiation, via tyrosine kinase receptors on target cells. The EGF receptor has a cytoplasmic tyrosine kinase domain, a transmembrane domain and an extracellular domain that binds to EGF. Ligand binding to the EGF receptor results in its dimerization, autophosphorylation and activation. Once activated, the EGF receptor transmits intracellular signals via the phosphorylation of several proteins.The activation of RAS by the EGF receptor is an important component in EGFsignaling. The guanine nucleotide exchange factor activates Ras which in turn triggers the Mitogen activated protein (MAP) kinase pathway. MAP kinases phosphorylate transfactors like activator protein 1 (AP-1) and Elk-1, leading to cellular growth and development. The phosphorylation of Janus kinases (JAK) by EGFR results in the activation of Signal transducers and activation of transcription proteins (STATs) which ultimately lead to cell growth and differentiation. Another key aspect of EGF signaling involves Phospholipase C gamma 1 (PLCγ1), which via inositol tri phosphate (IP3) results in Ca2+ release and activation of Protein Kinase C (PKC). PKC in turn phosphorylates and activates the transfactor Elk-1 which leads to cellular proliferation. Mutations in EGFR affecting its expression or activity are known to be involved in cancers, making EGFR an important drug target.This pathway highlights the important components of EGF signal transduction.