Self-phosphorylation of epidermal growth factor receptor: evidence for a model of intermolecular allosteric activation

Journal Article · Tue Mar 10 04:00:00 EST 1987 · Biochemistry; (United States)

DOI:https://doi.org/10.1021/bi00379a034· OSTI ID:6352524

Yarden, Y; Schlessinger, J

The membrane receptor for epidermal growth factor (EGF) is a 170,000 dalton glycoprotein composed of an extracellular EGF-binding domain and a cytoplasmic kinase domain connected by a stretch of 23 amino acids traversing the plasma membrane. The binding of EGF to the extracellular domain activates the cytoplasmic kinase function even in highly purified preparations of EGF receptor, suggesting that the activation occurs exclusively within the EGF receptor moiety. Conceivably, kinase activation may require the transfer of a conformational change through the single transmembrane region from the ligand binding domain to the cytoplasmic kinase region. Alternatively, ligand-induced receptor-receptor interactions may activate the kinase and thus bypass this requirement. Both mechanisms were contrasted by employing independent experimental approaches. On the basis of these results, an allosteric aggregation model is formulated for the activation of the cytoplasmic kinase function of the receptor by EGF. This model may be relevant to the mechanism by which the mitogenic signal of EGF is transferred across the membrane.

• Research Organization: Wiezmann Institute of Science, Rehovot, Israel
• OSTI ID: 6352524
• Journal Information: Biochemistry; (United States), Journal Name: Biochemistry; (United States) Vol. 26:5; ISSN BICHA
• Country of Publication: United States
• Language: English

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