Integrin alpha2beta1 mediates outside-in regulation of platelet spreading on collagen through activation of Src kinases and PLCgamma2.
Integrin alpha2beta1 mediates outside-in regulation of platelet spreading on collagen through activation of Src kinases and PLCgamma2.
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整联蛋白alpha2beta1通过激活SRC激酶和PLCGAMMA2介导胶原蛋白上血小板扩散的外部调节。
DOI：
10.1083/jcb.200208043
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发表时间：
2003-03-03
期刊：
影响因子：
--
通讯作者：
Watson SP
中科院分区：
文献类型：
--
作者：
Inoue O;Suzuki-Inoue K;Dean WL;Frampton J;Watson SP
胶原蛋白通过促进血管损伤部位血小板的粘附和活化在止血中起关键作用。在目前的血小板-胶原相互作用模型中，粘附通过整合素α2β1的由内而外调节和通过糖蛋白VI（GPVI）-Fc受体（FcR）γ链复合物的活化介导。本研究通过证明α2β1与胶原内的整合素特异性序列或胶原本身的结合产生基于酪氨酸激酶的细胞内信号，从而在不存在GPVI-FcR γ链复合物的情况下导致丝状伪足和板状伪足的形成来扩展该模型。血小板悬液中未发生相同事件。粘附血小板的α2β1活化刺激GPVI-FcR γ链级联中许多蛋白的酪氨酸磷酸化，包括Src、Syk、SLP-76和PLCγ2以及质膜钙ATP酶和粘着斑激酶。在Src激酶抑制剂PP 2存在下和PLCγ2缺陷型血小板中，α2β1介导的扩散被显著抑制。通过螯合细胞内的Ca 2+来消除扩散。血小板通过α2β1粘附于胶原蛋白产生细胞内信号的证明为控制血栓形成的机制提供了新的见解，并可能解释β1缺陷血栓的不稳定性质以及GPVI-FcR γ链复合物丢失对出血影响相对较小的原因。
Collagen plays a critical role in hemostasis by promoting adhesion and activation of platelets at sites of vessel injury. In the present model of platelet–collagen interaction, adhesion is mediated via the inside-out regulation of integrin α2β1 and activation through the glycoprotein VI (GPVI)–Fc receptor (FcR) γ-chain complex. The present study extends this model by demonstrating that engagement of α2β1 by an integrin-specific sequence from within collagen or by collagen itself generates tyrosine kinase–based intracellular signals that lead to formation of filopodia and lamellipodia in the absence of the GPVI–FcR γ-chain complex. The same events do not occur in platelet suspensions. α2β1 activation of adherent platelets stimulates tyrosine phosphorylation of many of the proteins in the GPVI–FcR γ-chain cascade, including Src, Syk, SLP-76, and PLCγ2 as well as plasma membrane calcium ATPase and focal adhesion kinase. α2β1-mediated spreading is dramatically inhibited in the presence of the Src kinase inhibitor PP2 and in PLCγ2-deficient platelets. Spreading is abolished by chelation of intracellular Ca2+. Demonstration that adhesion of platelets to collagen via α2β1 generates intracellular signals provides a new insight into the mechanisms that control thrombus formation and may explain the unstable nature of β1-deficient thrombi and why loss of the GPVI–FcR γ-chain complex has a relatively minor effect on bleeding.
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影响因子：
4.1
作者：
MORTON, LF;HARGREAVES, PG;BARNES, MJ
通讯作者：
BARNES, MJ
影响因子：
8.3
作者：
Blankenship, KA;Dawson, CB;Dean, WL
通讯作者：
Dean, WL
影响因子：
4.8
作者：
Jung, SM;Moroi, M
通讯作者：
Moroi, M
影响因子：
15.3
作者：
Massberg, S;Gawaz, M;Nieswandt, B
通讯作者：
Nieswandt, B
影响因子：
37.8
作者：
Goto, SY;Tamura, N;Takayama, H
通讯作者：
Takayama, H