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.
© 2012 John Wiley & Sons A/S.
Publication types
-
Research Support, N.I.H., Extramural
MeSH terms
-
Amyloid Precursor Protein Secretases / metabolism
-
Calpain / antagonists & inhibitors
-
Calpain / metabolism
-
Cell Line, Tumor
-
Cell Membrane / enzymology
-
Cell Membrane / metabolism
-
Cell Nucleus / metabolism
-
Epidermal Growth Factor / metabolism
-
ErbB Receptors / agonists
-
ErbB Receptors / antagonists & inhibitors
-
ErbB Receptors / metabolism*
-
Gene Expression
-
Glycoproteins / pharmacology
-
HEK293 Cells
-
Humans
-
Ionomycin / pharmacology
-
Proteolysis
-
Quinazolines / pharmacology
-
Serine Endopeptidases / biosynthesis
-
Serine Endopeptidases / metabolism
-
Serine Proteinase Inhibitors / pharmacology
-
Tyrphostins / pharmacology
Substances
-
Glycoproteins
-
Quinazolines
-
Serine Proteinase Inhibitors
-
Tyrphostins
-
calpain inhibitors
-
RTKI cpd
-
Ionomycin
-
Epidermal Growth Factor
-
ErbB Receptors
-
Amyloid Precursor Protein Secretases
-
Serine Endopeptidases
-
Calpain