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.

Barbero, S., Barila', D., Mielgo, A., Stagni, V., Clair, K., Stupack, D. (2008). Identification of a critical tyrosine residue in caspase 8 that promotes cell migration. THE JOURNAL OF BIOLOGICAL CHEMISTRY, 283(19), 13031-13034 [10.1074/jbc.M800549200].

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

BARILA', DANIELA;
2008-01-01

Abstract

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.
2008
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore BIO/18 - GENETICA
English
Con Impact Factor ISI
amino acids; animal cell culture; binding energy; binding sites; cell death; Caspase; catalytic activities; catalytic domains; cell migrations; cytosolic; do-mains; integrin; linker regions; migrating cells; programmed cell deaths; promotes cells; protease activities; src homology 2; tyrosine residues; cytology; caspase 8; green fluorescent protein; plasmid DNA; tyrosine; protein tyrosine kinase; animal cell; apoptosis; article; cell culture; cell death; cell migration; enzyme activity; enzyme localization; enzyme phosphorylation; fluorescence activated cell sorter; mouse; nonhuman; polyacrylamide gel electrophoresis; priority journal; cell adhesion; cell line; cell motion; genetics; human; metabolism; phosphorylation; Caspase 8; cell adhesion; cell line; cell movement; humans; phosphorylation; src-family kinase
Barbero, S., Barila', D., Mielgo, A., Stagni, V., Clair, K., Stupack, D. (2008). Identification of a critical tyrosine residue in caspase 8 that promotes cell migration. THE JOURNAL OF BIOLOGICAL CHEMISTRY, 283(19), 13031-13034 [10.1074/jbc.M800549200].
Barbero, S; Barila', D; Mielgo, A; Stagni, V; Clair, K; Stupack, D
Articolo su rivista
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/6406
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