Proteolytic cleavage of epidermal growth factor receptor by caspases

FEBS Letters

Bae, Sun Sik¹  Choi, Jang Hyun¹  Ryu, Sung Ho¹  Suh, Pann-Ghill¹  Oh, Yong Seok¹  Perry, David K.² 

[1] Department of Life Science, Division of Molecular and Life Science, Pohang University of Science and Technology, Pohang 790-784, South Korea;Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 29425, USA

关键词: Apoptosis;    Proteolysis;    Receptor;    PLC;    phospholipase C;    EGFR;    epidermal growth factor receptor;    PI3K;    phosphatidylinositol-3-kinase;    CHX;    cycloheximide;    TNF-α;    tumor necrosis factor-α;   

DOI  :  10.1016/S0014-5793(01)02167-6

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown