title: Regulated intramembrane cleavage of the EGF receptor.
abstract: Following the addition of EGF or ionomycin to A431 cells, protease activity mediates cleavage of the EGF receptor producing a 60 kDa fragment that includes the intracellular domain (ICD). This fragment is located in both membrane and nuclear fractions. On the basis of sensitivity to chemical inhibitors and overexpression of cDNAs, the rhomboid intramembrane proteases, not γ-secretase proteases, are identified as responsible for the cleavage event. Agonist-initiated cleavage occurs slowly over 3-24 h. Inhibition of calpain protease activity significantly increased the detectable level of ICD fragment.
authors.affiliation: Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232-0146, USA.
authors.forename: Hong-Jun
authors.initials: HJ
authors.lastname: Liao
authors.forename: Graham
authors.initials: G
authors.lastname: Carpenter
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D002154:Calpain / Q000037:antagonists & inhibitors / Q000378:metabolism; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000201:enzymology / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015870:Gene Expression; D006023:Glycoproteins / Q000494:pharmacology; D057809:HEK293 Cells; D006801:Humans; D015759:Ionomycin / Q000494:pharmacology; D059748:Proteolysis; D011799:Quinazolines / Q000494:pharmacology; D012697:Serine Endopeptidases / Q000096:biosynthesis / Q000378:metabolism; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D020032:Tyrphostins / Q000494:pharmacology
chemical_list: D006023:Glycoproteins; D011799:Quinazolines; D015842:Serine Proteinase Inhibitors; D020032:Tyrphostins; C039304:calpain inhibitors; C101044:RTKI cpd; D015759:Ionomycin; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D053829:Amyloid Precursor Protein Secretases; D012697:Serine Endopeptidases; D002154:Calpain