Fyn and Lyn phosphorylate the Fc receptor gamma chain downstream of glycoprotein VI in murine platelets, and Lyn regulates a novel feedback pathway.
Fyn and Lyn phosphorylate the Fc receptor gamma chain downstream of glycoprotein VI in murine platelets, and Lyn regulates a novel feedback pathway.
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DOI：
10.1182/blood.v96.13.4246.h8004246_4246_4253
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发表时间：
2000-12
期刊：
影响因子：
20.3
通讯作者：
Lynn Quek;J. Pasquet;Ingeborg Hers;R. Cornall;Graham Knight;Mike Barnes;Margaret L. Hibbs;Ashley R. Dunn;Clifford A. Lowell;Steve P. Watson
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文献类型：
--
作者：
Lynn Quek;J. Pasquet;Ingeborg Hers;R. Cornall;Graham Knight;Mike Barnes;Margaret L. Hibbs;Ashley R. Dunn;Clifford A. Lowell;Steve P. Watson
胶原蛋白对血小板的活化由复合糖蛋白VI（GPVI）/Fc受体γ（FcR γ链）介导。在目前的研究中，2个Src家族激酶，Fyn和林恩，在GPVI信号转导的作用已被检查使用小鼠血小板缺乏一个或两个激酶。在fyn（-/-）血小板中，FcR γ链的酪氨酸磷酸化、磷脂酶C（PLC）活性、聚集和分泌减少，但反应开始的时间不变。在lyn（-/-）血小板中，酪氨酸磷酸化和功能反应的发生延迟长达30秒，随后磷酸化恢复，聚集和α颗粒分泌增强。在fyn（-/-）lyn（-/-）双突变体血小板中，胶原相关肽刺激引起的酪氨酸磷酸化和聚集反应进一步减弱和延迟，未观察到增强作用。本研究首次提供了Fyn和林恩介导GPVI连接后FcR免疫受体酪氨酸激活基序磷酸化和PLC γ 2激活的遗传学证据。林恩通过一种未表征的抑制途径在抑制血小板活化中发挥额外的作用。（血。2000; 96：4246 - 4253）
Activation of platelets by collagen is mediated by the complex glycoprotein VI (GPVI)/Fc receptor gamma (FcR gamma chain). In the current study, the role of 2 Src family kinases, Fyn and Lyn, in GPVI signaling has been examined using murine platelets deficient in one or both kinases. In the fyn(-/-) platelets, tyrosine phosphorylation of FcR gamma chain, phopholipase C (PLC) activity, aggregation, and secretion are reduced, though the time of onset of response is unchanged. In the lyn(-/-) platelets, there is a delay of up to 30 seconds in the onset of tyrosine phosphorylation and functional responses, followed by recovery of phosphorylation and potentiation of aggregation and alpha-granule secretion. Tyrosine phosphorylation and aggregation in response to stimulation by collagen-related peptide is further attenuated and delayed in fyn(-/-)lyn(-/-) double-mutant platelets, and potentiation is not seen. This study provides the first genetic evidence that Fyn and Lyn mediate FcR immune receptor tyrosine-based activation motif phosphorylation and PLC gamma 2 activation after the ligation of GPVI. Lyn plays an additional role in inhibiting platelet activation through an uncharacterized inhibitory pathway. (Blood. 2000;96:4246-4253)