Identification of a critical tyrosine residue in caspase 8 that promotes cell migration

Simone Barbero, Daniela Barilà, Ainhoa Mielgo, Venturina Stagni, Kiran Clair, Dwayne Stupack

Research output: Contribution to journalArticlepeer-review


Caspase 8 is a critical upstream initiator of programmed cell death but, paradoxically, has also been shown to promote cell migration. Here, we show that tyrosine 380 in the linker loop of human caspase 8 is a critical switch determining caspase 8 function. Our studies show that, in addition to its cytosolic distribution, caspase 8 is recruited to lamella of migrating cells. Although the catalytic domain of caspase 8 is sufficient for recruitment and promotion of cell migration, catalytic activity per se is not required. Instead, we find that integrin-mediated adhesion promotes caspase 8 phosphorylation on tyrosine 380. Accordingly, mutation of this site compromises localization to the periphery and the potentiation of cell migration. Mechanistically, this linker region of caspase 8 acts as a Src homology 2 binding site. In particular, tyrosine 380 is critical for interaction with Src homology 2 domains. The results identify a novel mechanism by which caspase 8 is recruited to the lamella of a migrating cell, promoting cell migration independent of its protease activity.

Original languageEnglish
Pages (from-to)13031-13034
Number of pages4
JournalJournal of Biological Chemistry
Issue number19
Publication statusPublished - May 9 2008

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology


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