Proteolysis of the epidermal growth factor receptor by endogenous calcium-activated neutral protease from rat liver.
In A-431 membranes but not in rat liver membranes, the epidermal growth factor (EGF) receptor was converted from a Mr=180,000 to a Mr=160,000 form by a protease activated when cells were broken in the presence of calcium. Calcium-activated neutral protease (CANP) activity in rat liver cytosol was separated from its protein inhibitor by DEAE-cellulose chromatography. When fractions containing this protease activity were incubated with rat liver membranes in the presence of calcium, the Mr=180,000 form of the receptor was converted to the Mr=160,000 form. This conversion was blocked both by the separated endogenous inhibitor and by leupeptin. Apparently CANP is a highly regulated endogenous protease which could degrade the EGF receptor-kinase in most tissues.
D000818:Animals; D002154:Calpain; D010450:Endopeptidases / Q000378:metabolism*; D066246:ErbB Receptors; D007976:Leupeptins / Q000494:pharmacology; D008099:Liver / Q000201:enzymology*; D008297:Male; D008970:Molecular Weight; D010766:Phosphorylation; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000378:metabolism*
D007976:Leupeptins; D011956:Receptors, Cell Surface; D066246:ErbB Receptors; D010450:Endopeptidases; D002154:Calpain; C032854:leupeptin