Distinct domains of αIIbβ3 support different aspects of outside-in signal transduction and platelet activation induced by LSARLAF, an αIIbβ3 interacting peptide
Distinct domains of αIIbβ3 support different aspects of outside-in signal transduction and platelet activation induced by LSARLAF, an αIIbβ3 interacting peptide
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DOI：
10.1055/s-0037-1616147
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发表时间：
2001-09-01
影响因子：
6.7
通讯作者：
Gartner, TK
中科院分区：
文献类型：
--
作者：
Derrick, JM;Shattil, SJ;Gartner, TK
肽LSARLAF引起α II β 3依赖性血小板活化，例如分泌、聚集、铺展和粘附在纤维蛋白原上以及酪氨酸磷酸化。在缺乏整联蛋白β 3亚基（α IIb β 3 δ 724）的大部分胞质结构域的变体血小板中研究了由LSARLAF诱导的α IIb β 3依赖性外向内信号转导。这些研究表明，这种α IIb β 3依赖性外向内信号转导的仅某些方面受到β 3截短的影响。具体而言，α IIb β 3 Delta 724支持LSARLAF诱导的血小板聚集、凝集和分泌，但未能触发细胞骨架重组和血小板在纤维蛋白原上的铺展。尽管事实上PMA诱导的非α IIb β 3介导的信号传导导致这些血小板在纤维蛋白原上扩散。因此，需要不同的α IIb β 3结构域来支持LSARLAF诱导的血小板活化的不同方面。此外，这些研究表明，并非所有α IIb β 3依赖性血小板反应都需要完整的β 3胞质尾区。
The peptide LSARLAF causes alpha II beta3-dependent platelet activation exemplified by secretion, aggregation, spreading and adhesion on fibrinogen, and tyrosine phosphorylation. alpha IIb beta3-dependent outside-in signal transduction induced by LSARLAF was investigated in variant thrombasthenic platelets which lack most of the cytoplasmic domain of the integrin beta3 subunit ((alpha IIb beta3 Delta 724), These studies revealed that only certain aspects of this alpha IIb beta3-dependent outside-in signaling were affected by the beta3 truncation. Specifically, alpha IIb beta3 Delta 724 supported LSARLAF-induced platelet aggregation, agglutination and secretion, but failed to trigger cytoskeletal reorganization and platelet spreading on fibrinogen. despite the fact that PMA-induced non alpha IIb beta3 mediated signaling caused spreading of these platelets on fibrinogen. Thus, distinct domains of alpha IIb beta3 are required to support different aspects of LSARLAF-induced platelet activation. Furthermore, these studies suggest ;that not all alpha IIb beta3-dependent platelet responses require an intact beta3 cytoplasmic tail.