Proteolytic cleavage of epidermal growth factor receptor. A Ca2+-dependent, sulfhydryl-sensitive proteolytic system in A431 cells.

摘要: Abstract The Mr = 160,000 epidermal growth factor (EGF) receptor in A431 cells is partially cleaved during membrane isolation to a 145,000 polypeptide containing both EGF binding and phosphate acceptor sites. We show that the proteolytic degradation of depends upon presence Ca2+ medium used scrape from substratum. Only high molecular weight form detected membranes prepared absence Ca2+. Ca2+-dependent proteolysis occurs rapidly (t1/2 approximately 5 min) following cell scraping. Proteolysis results decrease EGF-dependent phosphorylation while retaining capacity. In addition, uncleaved reveal substantial increase proteins with 80, 89, 185 X 10(3). Ca2+, addition iodoacetic acid scraping strongly inhibits fragmentation, whereas other inhibitors (phenylmethylsulfonyl fluoride, leupeptin, pepstatin) have no effect. implicate role for Ca2+-dependent, SH-sensitive protease degradation. Prevention yields preparations highly active kinase system.