Epidermal growth factor receptor

The EGF receptor (. Abbreviation of Epidermal Growth Factor Receptor, EGFR) is a protein found in cell membranes of vertebrates; it is the receptor for the epidermal growth factor ( EGF) and is a member of the ErbB family, a subfamily of four closely related receptor tyrosine kinases: EGFR1/HER1 (ErbB -1), HER2/c-neu (ErbB- 2), HER3 (ErbB -3), and HER4 (ErbB -4).

The EGF receptor is a transmembrane receptor with intrinsic tyrosine kinase activity which occurs in humans in all cell types. The receptor has only a single membrane passage and in the cytoplasmic part of a kinase domain with ATP - binding site. The activation ( dimerization ) of the EGFR occurs by extracellular binding of the ligands epidermal growth factor (EGF) and transforming growth factor ( TGFa ), the signal of which he leads on autophosphorylation and the recruitment of signaling molecules such as Akt / PKB, MEK or STAT protein to the cell interior ( signaling ), which ultimately stimulate cell growth, and prevent the apoptotic (programmed) cell death. The EGF receptor is thus one of the receptors for growth factors.

1,25 (OH) 2D3 inhibits the receptor - ligand complex, which may contribute to the efficacy of Vitamin D in the treatment of psoriasis, psoriatic cells form because increased TGFa.

The EGF receptor is upregulated in various tumor types and / or present in mutated form, which means that the tumor cells grow and multiply uncontrollably. As a result, it may result in an increased formation of metastases. Further, it is also less sensitive to chemotherapy and radiotherapy.

Novel cancer therapies aim to block this oncogenic signal of EGFR and thus to suppress tumor growth. Already successfully tested and approved substances of this so-called targeted cancer therapy ( engl. targeted therapy ) include gefitinib ( Iressa ), erlotinib ( Tarceva) or the monoclonal antibody cetuximab (Erbitux ) and panitumumab ( Vectibix ).

Protein structure

The structure of the EGFR - monomer comprises:

  • The ectodomain (extracellular domain ) with two homologous domains I ( L1 ) and III ( L2) and the cysteine-rich domains II (CR1 or S1 ) and IV ( CR2 or S2 )
  • A single-pass transmembrane α -helix
  • The catalytic region in the cytoplasm of the tyrosine kinase accompanied by juxtamembrane and C -terminal regulatory region.

So far, the overall structure of the dimer is unknown, but parts have been greatly already determined: domains I-III and a few remnants of domain IV ( single crystal), the juxtamembrane region alone (NMR ) or together with the tyrosine kinase ( single crystal) and the tyrosine kinase alone ( single crystal).

Protein isoform Human Genome Organisation HER2/neu Proteinkinase B Dimer (chemistry) Cancer Letters
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