Src kinase phosphorylates Caspase-8 on Tyr380: A novel mechanism of apoptosis suppression

Silvia Cursi, Alessandra Rufini, Venturina Stagni, Ivano Condò, Vittoria Matafora, Angela Bachi, Antonio Paniccià Bonifazi, Luigi Coppola, Giulio Superti-Furga, Roberto Testi, Daniela Barilà

Research output: Contribution to journalArticle

Abstract

We identified Caspase-8 as a new substrate for Src kinase. Phosphorylation occurs on Tyr380, situated in the linker region between the large and the small subunits of human Procaspase-8, and results in downregulation of Caspase-8 proapoptotic function. Src activation triggers Caspase-8 phosphorylation on Tyr380 and impairs Fas-induced apoptosis. Accordingly, Src failed to protect Caspase-8-defective human cells in which a Caspase-8-Y380F mutant is expressed from Fas-induced cell death. Remarkably, Src activation upon EGF-receptor stimulation triggers endogenous Caspase-8 phosphorylation and prevents Fas-induced apoptosis. Tyr380 is phosphorylated also in human colon cancers where Src is aberrantly activated. These data provide the first evidence for a direct role of tyrosine phosphorylation in the control of caspases and reveal a new mechanism through which tyrosine kinases inhibit apoptosis and participate in tumor progression.

Original languageEnglish
Pages (from-to)1895-1905
Number of pages11
JournalEMBO Journal
Volume25
Issue number9
DOIs
Publication statusPublished - May 3 2006

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Keywords

  • Apoptosis
  • Cancer
  • Caspase-8
  • Fas-receptor
  • Src non-receptor tyrosine kinase

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Cursi, S., Rufini, A., Stagni, V., Condò, I., Matafora, V., Bachi, A., Bonifazi, A. P., Coppola, L., Superti-Furga, G., Testi, R., & Barilà, D. (2006). Src kinase phosphorylates Caspase-8 on Tyr380: A novel mechanism of apoptosis suppression. EMBO Journal, 25(9), 1895-1905. https://doi.org/10.1038/sj.emboj.7601085