FEBS letters, 2001-02, Vol.491 (1), p.16-20
2001
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Details
- Autor(en) / Beteiligte
- Titel
- Proteolytic cleavage of epidermal growth factor receptor by caspases
- Ist Teil von
- FEBS letters, 2001-02, Vol.491 (1), p.16-20
- Ort / Verlag
- England: Elsevier B.V
- Erscheinungsjahr
- 2001
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0014-5793eISSN: 1873-3468DOI: 10.1016/S0014-5793(01)02167-6Titel-ID: cdi_proquest_miscellaneous_70652402
- Format
- –
- Schlagworte
- Amino Acid Chloromethyl Ketones - pharmacology, Amino Acid Sequence, Apoptosis, Caspase 1 - metabolism, Caspase 2, Caspase 3, Caspase 7, Caspase Inhibitors, Caspases - metabolism, CHX, cycloheximide, Cysteine Proteinase Inhibitors - pharmacology, EGFR, epidermal growth factor receptor, ErbB Receptors - metabolism, Humans, Isoenzymes - metabolism, Molecular Sequence Data, Oligopeptides - pharmacology, Peptide Hydrolases - metabolism, Phospholipase C gamma, Phosphorylation, PI3K, phosphatidylinositol-3-kinase, PLC, phospholipase C, Proteolysis, Receptor, TNF-α, tumor necrosis factor-α, Tumor Cells, Cultured, Tumor Necrosis Factor-alpha - metabolism, Tumor Necrosis Factor-alpha - pharmacology, Type C Phospholipases - metabolism, Tyrosine - metabolism