Mechanism of epidermal growth factor receptor autophosphorylation and high-affinity binding.

AUTOR(ES)

Böni-Schnetzler, M

RESUMO

Epidermal growth factor (EGF) receptor monomers and noncovalently associated dimers were isolated by sucrose density gradient centrifugation, and their respective binding and autophosphorylation activities were determined. We find that monomers are low-affinity receptors and dimers are high-affinity receptors. In the absence of EGF, dimers exhibit a 4-fold higher autophosphorylation activity than do monomers. Addition of EGF increases autophosphorylation on monomers an average of 4.8-fold but has a minimal effect on autophosphorylation of dimers. Furthermore, EGF binding shifts the receptor monomer-dimer equilibrium to the dimer form. We conclude that EGF stimulates in vitro receptor autophosphorylation by inducing kinase-inactive receptor monomers to associate and form receptor dimers, in which conformation the autophosphorylation activity is enhanced.

Documentos Relacionados

• High-affinity RNA ligands to basic fibroblast growth factor inhibit receptor binding.
• High-affinity interleukin 2 binding by an oncogenic hybrid interleukin 2-epidermal growth factor receptor molecule.
• Progesterone receptor subunits are high-affinity substrates for phosphorylation by epidermal growth factor receptor.
• Growth stimulation of A431 cells by epidermal growth factor: identification of high-affinity receptors for epidermal growth factor by an anti-receptor monoclonal antibody.
• Epidermal growth factor: Biological activity requires persistent occupation of high-affinity cell surface receptors