Tyrosine phosphorylation of the integrin β3 subunit regulates β3 cleavage by calpain
Tyrosine phosphorylation of the integrin β3 subunit regulates β3 cleavage by calpain
复制标题
DOI：
10.1074/jbc.c600039200
复制
发表时间：
2006-10-06
影响因子：
4.8
通讯作者：
Du, Xiaoping
中科院分区：
文献类型：
--
作者：
Xi, Xiaodong;Flevaris, Panagiotis;Du, Xiaoping
β(3)整合素的外向内信号传导诱导并需要β(3)亚基上酪氨酸747 （Tyr(747)）和酪氨酸759 （Tyr(759)）的磷酸化，但这一要求的机制尚不清楚。另一方面，整合素信号传导的一个关键结果，细胞扩散，被钙蛋白酶切割β(3)细胞质结构域所抑制。我们发现-(3)酪氨酸磷酸化抑制钙蛋白酶裂解。将两种酪氨酸突变为苯丙氨酸使β(3)对钙蛋白酶裂解敏感。此外，在黏附位点和血小板扩散前沿β(3)的Tyr（747）和Tyr（759）磷酸化受到不同的调控。Tyr（759）的选择性去磷酸化与Tyr（759）的calpain裂解有关。因此，酪氨酸磷酸化促进整合素信号传导和细胞扩散的一种机制是它抑制钙蛋白酶在细胞质域β(3)的切割。
Outside-in signaling of beta(3) integrins induces and requires phosphorylation at tyrosine 747 (Tyr(747)) and tyrosine 759 (Tyr(759)) of the beta(3) 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 beta(3) cytoplasmic domain. Here we show that beta(3) tyrosine phosphorylation inhibits calpain cleavage. Mutating both tyrosines to phenylalanine sensitizes beta(3) to calpain cleavage. Furthermore, phosphorylation at Tyr(747) and Tyr(759) of beta(3) in the focal adhesion sites and the leading edge of spreading platelets was differentially regulated. Selective dephosphorylation of Tyr(759) is associated with calpain cleavage at Tyr(759). Thus, one mechanism by which tyrosine phosphorylation promotes integrin signaling and cell spreading is its inhibition of calpain cleavage of the beta(3) cytoplasmic domain.