Proteolytic cleavage of epidermal growth factor receptor by caspases
- 20 February 2001
- journal article
- Published by Wiley in FEBS Letters
- Vol. 491 (1-2) , 16-20
- https://doi.org/10.1016/s0014-5793(01)02167-6
Abstract
Apoptotic proteases cleave and inactivate survival signaling molecules such as Akt/PKB, phospholipase C (PLC)-γ1, and Bcl-2. We have found that treatment of A431 cells with tumor necrosis factor-α in the presence of cycloheximide resulted in the cleavage of epidermal growth factor receptor (EGFR) as well as the activation of caspase-3. Among various caspases, caspase-1, caspase-3 and caspase-7 were most potent in the cleavage of EGFR in vitro. Proteolytic cleavage of EGFR was inhibited by both YVAD-cmk and DEVD-fmk in vitro. We also investigated the effect of caspase-dependent cleavage of EGFR upon the mediation of signals to downstream signaling molecules such as PLC-γ1. Cleavage of EGFR by caspase-3 significantly impaired the tyrosine phosphorylation of PLC-γ1 in vitro. Given these results, we suggest that apoptotic protease specifically cleaves and inactivates EGFR, which plays crucial roles in anti-apoptotic signaling, to abrogate the activation of EGFR-dependent downstream survival signaling molecules.Keywords
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