TY - JOUR
T1 - Tyrosine phosphorylation of the integrin β3 subunit regulates β3 cleavage by calpain
AU - Xi, Aodong
AU - Flevaris, Panagiotis
AU - Stojanovic, Aleksandra
AU - Chishti, Athar
AU - Phillips, David R.
AU - Lam, Stephen C.T.
AU - Du, Xiaoping
N1 - Copyright:
Copyright 2011 Elsevier B.V., All rights reserved.
PY - 2006/10/6
Y1 - 2006/10/6
N2 - 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.
AB - 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.
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U2 - 10.1074/jbc.C600039200
DO - 10.1074/jbc.C600039200
M3 - Article
C2 - 16935858
AN - SCOPUS:33749582751
VL - 281
SP - 29426
EP - 29430
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 40
ER -