A molecular switch that controls cell spreading and retraction

Panagiotis Flevaris, Aleksandra Stojanovic, Haixia Gong, Athar Chishti, Emily Welch, Xiaoping Du*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

116 Scopus citations

Abstract

Integrin-dependent cell spreading and retraction are required for cell adhesion, migration, and proliferation, and thus are important in thrombosis, wound repair, immunity, and cancer development. It remains unknown how integrin outside-in signaling induces and controls these two opposite processes. This study reveals that calpain cleavage of integrin β3 at Tyr 759 switches the functional outcome of integrin signaling from cell spreading to retraction. Expression of a calpain cleavage-resistant β3 mutant in Chinese hamster ovary cells causes defective clot retraction and RhoA-mediated retraction signaling but enhances cell spreading. Conversely, a calpain-cleaved form of β3 fails to mediate cell spreading, but inhibition of the RhoA signaling pathway corrects this defect. Importantly, the calpain-cleaved β3 fails to bind c-Src, which is required for integrin-induced cell spreading, and this requirement of β3-associated c-Src results from its inhibition of RhoA-dependent contractile signals. Thus, calpain cleavage of β3 at Tyr759 relieves c-Src-mediated RhoA inhibition, activating the RhoA pathway that confines cell spreading and causes cell retraction.

Original languageEnglish (US)
Pages (from-to)553-565
Number of pages13
JournalJournal of Cell Biology
Volume179
Issue number3
DOIs
StatePublished - Nov 5 2007

ASJC Scopus subject areas

  • Cell Biology

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