Quek L S, Pasquet J M, Hers I, Cornall R, Knight G, Barnes M, Hibbs M L, Dunn A R, Lowell C A, Watson S P
Department of Pharmacology, University of Oxford, United Kingdom.
Blood. 2000 Dec 15;96(13):4246-53.
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)
胶原蛋白对血小板的激活作用是由复合糖蛋白VI（GPVI）/Fc受体γ链（FcRγ链）介导的。在本研究中，利用缺乏一种或两种激酶的小鼠血小板，研究了两种Src家族激酶Fyn和Lyn在GPVI信号传导中的作用。在Fyn基因敲除（fyn(-/-)）的血小板中，FcRγ链的酪氨酸磷酸化、磷脂酶C（PLC）活性、聚集和分泌均降低，不过反应起始时间未变。在Lyn基因敲除（lyn(-/-)）的血小板中，酪氨酸磷酸化和功能反应的起始延迟长达30秒，随后磷酸化恢复，聚集和α-颗粒分泌增强。在fyn(-/-)lyn(-/-)双突变血小板中，对胶原相关肽刺激的酪氨酸磷酸化和聚集进一步减弱和延迟，且未见增强现象。本研究提供了首个遗传学证据，表明Fyn和Lyn在GPVI连接后介导基于免疫受体酪氨酸激活基序的FcR磷酸化和PLCγ2激活。Lyn通过一条未明确的抑制途径在抑制血小板激活中发挥额外作用。（《血液》。2000年；96:4246 - 4253）
