Critical roles for the COOH-terminal NITY and RGT sequences of the integrin beta3 cytoplasmic domain in inside-out and outside-in signaling.
Critical roles for the COOH-terminal NITY and RGT sequences of the integrin beta3 cytoplasmic domain in inside-out and outside-in signaling.
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DOI：
10.1083/jcb.200303120
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发表时间：
2003-07-21
期刊：
影响因子：
--
通讯作者：
Du X
中科院分区：
文献类型：
--
作者：
Xi X;Bodnar RJ;Li Z;Lam SC;Du X
整合素αIIbβ3的双向信号传导需要β3胞质结构域。为了确定对整联蛋白信号传导至关重要的β3胞质结构域中的序列，建立了共表达血管性血友病因子（vWF）血小板受体、糖蛋白Ib-IX、整联蛋白αIIb和在T741、Y 747、F754和Y 759的COOH末端位点截短的β3突变体的细胞系。截短Y 759不影响整合素活化，如vWF诱导的纤维蛋白原结合所示，但影响细胞铺展和稳定粘附。因此，β3的COOH-末端RGT序列对于由外向内信号传导而不是由内向外信号传导是重要的。相反，在F754、Y 747或T741处的截短完全消除了整合素活化。用丙氨酸取代Y 759的点突变也消除了整合素活化。因此，含有NXXY基序的β3的T755 NITY 759序列对于由内而外的信号传导至关重要，而完整的COOH末端对于由外向内的信号传导至关重要。此外，我们发现钙依赖性蛋白酶calpain在血小板聚集和粘附过程中优先切割β3群体中的Y 759，这表明calpain可能选择性地调节整合素由外向内的信号传导。
Bidirectional signaling of integrin αIIbβ3 requires the β3 cytoplasmic domain. To determine the sequence in the β3 cytoplasmic domain that is critical to integrin signaling, cell lines were established that coexpress the platelet receptor for von Willebrand factor (vWF), glycoprotein Ib-IX, integrin αIIb, and mutants of β3 with truncations at sites COOH terminal to T741, Y747, F754, and Y759. Truncation at Y759 did not affect integrin activation, as indicated by vWF-induced fibrinogen binding, but affected cell spreading and stable adhesion. Thus, the COOH-terminal RGT sequence of β3 is important for outside-in signaling but not inside-out signaling. In contrast, truncation at F754, Y747, or T741 completely abolished integrin activation. A point mutation replacing Y759 with alanine also abolished integrin activation. Thus, the T755NITY759 sequence of β3, containing an NXXY motif, is critical to inside-out signaling, whereas the intact COOH terminus is important for outside-in signaling. In addition, we found that the calcium-dependent protease calpain preferentially cleaves at Y759 in a population of β3 during platelet aggregation and adhesion, suggesting that calpain may selectively regulate integrin outside-in signaling.
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分析使用重构的哺乳动物细胞表达模型，对整联蛋白α（IIB）β（3）的血小板糖蛋白IB-IX介导的激活的作用分析。
影响因子：
7.8
作者：
Gu, M;Xi, X;Englund, G D;Berndt, M C;Du, X
通讯作者：
Du, X
影响因子：
7.8
作者：
Bialkowska, K;Kulkarni, S;Fox, JEB
通讯作者：
Fox, JEB
DOI：
10.1083/jcb.111.6.3117
发表时间：
1990-12
期刊：
The Journal of cell biology
影响因子：
--
作者：
Golden A;Brugge JS;Shattil SJ
通讯作者：
Shattil SJ
影响因子：
4.8
作者：
Englund, GD;Bodnar, RJ;Du, XP
通讯作者：
Du, XP
影响因子：
5.3
作者：
Azam, M;Andrabi, SS;Chishti, AH
通讯作者：
Chishti, AH