Peptide LSARLAF induces integrin β3 dependent outside-in signaling in platelets.
Peptide LSARLAF induces integrin β3 dependent outside-in signaling in platelets.
复制标题
肽 LSARLAF 诱导血小板中整合素 β3 依赖性外向内信号传导。
DOI：
10.1016/j.thromres.2012.03.004
复制
发表时间：
2012-08
影响因子：
7.5
通讯作者：
Gartner TK
中科院分区：
文献类型：
--
作者：
Niu H;Xu Z;Li D;Zhang L;Wang K;Taylor DB;Liu J;Gartner TK
肽LSARLAF（LSA）可以在没有“由内而外”信号的情况下结合并激活整合素αIIbβ3。活性αIIbβ3介导“由外向内”信号传导，促进血小板聚集、颗粒分泌和TxA 2产生。在此，我们鉴定了除αIIbβ3外介导LSA诱导的血小板活化的膜糖蛋白，并确定了Src、PLCγ2、FcRγ链和SLP-76在LSA诱导的血小板活化中的作用。进行配体-受体结合分析以研究肽LSA或其对照肽FRALASL（FRA）对整合素与其配体结合的影响。在LSA或FRA存在下，测量表达αIIbβ3或αVβ3的CHO细胞在固定化纤维蛋白原上的铺展。检测洗涤的β3、Src、FcRγ链、LAT和SLP-76缺陷型血小板对LSA的反应性聚集和分泌。配体-受体结合实验表明，LSA可促进多种配体与αIIbβ3或αVβ3的结合。LSA还增强了CHO细胞在固定化纤维蛋白原上αIIbβ3或αVβ3的表达。β3缺陷型血小板不能聚集和分泌响应LSA。PLCγ2和Syk的磷酸化也具有β3依赖性。Src、FcRγ链、LAT和SLP-76缺陷型血小板对LSA无聚集、分泌ATP和产生TxA 2的反应。LSA诱导的血小板活化是β3依赖性的，信号分子Src、FcRγ链、SLP-76和LAT在LSA诱导的β3介导的信号转导中起关键作用。
Peptide LSARLAF (LSA) can bind and activate integrin αIIbβ3 in the absence of ‘inside-out’ signal. The active αIIbβ3 mediates ‘outside-in’ signaling that elicits platelet aggregation, granule secretion and TxA2 production. Here we identify the membrane glycoproteins which mediate LSA-induced platelet activation other than αIIbβ3, and determine the roles of Src, PLCγ2, FcRγ-chain, and SLP-76 in LSA-induced platelet activation. Ligand-receptor binding assay was performed to study the effect of peptide LSA or its control peptide FRALASL (FRA) on integrins binding to their ligands. Spreading of CHO cells expressing αIIbβ3 or αVβ3 on immobilized fibrinogen was measured in the presence of LSA or FRA. Washed β3, Src, FcRγ-chain, LAT and SLP-76 deficient platelets aggregation and secretion were tested in response to LSA. Ligand-receptor binding assay indicated that LSA promoted the binding of multiple ligands to αIIbβ3 or αVβ3. LSA also enhanced CHO cells with αIIbβ3 or αVβ3 expression spreading on immobilized fibrinogen. β3 deficient platelets failed to aggregate and secrete in response to LSA. The phosphorylation of PLCγ2 and Syk was also β3 dependent. Src, FcRγ-chain, LAT and SLP-76 deficient platelets did not aggregate, secrete ATP or produce TxA2 in response to LSA. LSA-induced platelet activation is β3 dependent, and signaling molecules Src, FcRγ-chain, SLP-76 and LAT play crucial roles in LSA-induced β3 mediated signaling.
登录
查看更多内容
影响因子：
6.7
作者：
Derrick, JM;Shattil, SJ;Gartner, TK
通讯作者：
Gartner, TK
影响因子：
30.5
作者：
Mocsai, Attila;Abram, Clare L.;Lowell, Clifford A.
通讯作者：
Lowell, Clifford A.
DOI：
10.1083/jcb.200703185
发表时间：
2007-11-05
期刊：
The Journal of cell biology
影响因子：
--
作者：
Flevaris P;Stojanovic A;Gong H;Chishti A;Welch E;Du X
通讯作者：
Du X
影响因子：
20.3
作者：
Basani, RB;French, DL;Poncz, M
通讯作者：
Poncz, M
影响因子：
4.1
作者：
Briddon, SJ;Watson, SP
通讯作者：
Watson, SP