Molecular Mechanism of Mitogen Action: Processing of Receptor Induced by Epidermal Growth Factor

摘要: Abstract An affinity labeling technique used previously for identification of a membrane receptor epidermal growth factor (EGF) was exploited to investigate the physiological fate after binding EGF. Incubation affinity-labeled cells at 37° resulted in time-dependent loss radioactivity from EGF-receptor covalent complex (Mr 190,000). Ninety percent lost band Mr 190,000 during 1-hr incubation appeared three bands 62,000, 47,000, and 37,000. The crosslinked 190,000) on intact accessible action trypsin 4° cofractionated with plasmalemmal fraction. proteolytic processing products were inaccessible banded lysosomal fraction upon subcellular fractionation. rate internalization radiolabeled same as reduction activity induced by A study relationship between EGF-induced processing, stimulation DNA synthesis, showed that both these processes half-maximally stimulated approximately 0.1 nM EGF, concentration which only 10% sites are occupied. These data indicate concentrations EGF subsaturating but optimal biological activity, there is slow, continuous process degradation could be limiting mitogenesis.