Tyrosine phosphorylation of the integrin β3 subunit regulates β3 cleavage by calpain

Aodong Xi, Panagiotis Flevaris, Aleksandra Stojanovic, Athar Chishti, David R. Phillips, Stephen C.T. Lam, Xiaoping Du*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

47 Scopus citations


Outside-in signaling of β3 integrins induces and requires phosphorylation at tyrosine 747 (Tyr747) and tyrosine 759 (Tyr 759) of the β3 subunit, but the mechanism for this requirement is unclear. On the other hand, a key consequence of integrin signaling, cell spreading, is inhibited by calpain cleavage of β3 cytoplasmic domain. Here we show that β3 tyrosine phosphorylation inhibits calpain cleavage. Mutating both tyrosines to phenylalanine sensitizes β3 to calpain cleavage. Furthermore, phosphorylation at Tyr747 and Tyr759 of β3 in the focal adhesion sites and the leading edge of spreading platelets was differentially regulated. Selective dephosphorylation of Tyr759 is associated with calpain cleavage at Tyr759. Thus, one mechanism by which tyrosine phosphorylation promotes integrin signaling and cell spreading is its inhibition of calpain cleavage of the β3 cytoplasmic domain.

Original languageEnglish (US)
Pages (from-to)29426-29430
Number of pages5
JournalJournal of Biological Chemistry
Issue number40
StatePublished - Oct 6 2006

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry
  • Cell Biology


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