Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) regulates collagen-mediated platelet activation through its cytoplasmic immunoreceptor tyrosine-based inhibition motifs (ITIMs). However, the function of CEACAM1's extracellular cleavage fragments is currently unknown. In the present study, we used mass spectrometry (MS) to identify 9 cleavage fragments shed by matrix metallopeptidase 12 (MMP-12), and then we synthesized peptides with sequences corresponding to the fragments. QLSNGNRTLT (QLSN), a peptide from the A1-domain of CEACAM1, significantly attenuated collagen-induced platelet aggregation. QLSN also attenuated platelet static adhesion to collagen. Additionally, QLSN reduced human platelet secretion and integrin αIIbβ3 activation in response to glycoprotein VI (GPVI)-selective agonist, convulxin. Correspondingly, QLSN treatment significantly decreased convulxin-mediated phosphorylation of Src, protein kinase B (Akt), spleen tyrosine kinase (Syk) and phospholipase Cγ2 (PLCγ2) in human platelets. These data indicate that the CEACAM1-derived peptide QLSN inhibits GPVI-mediated human platelet activation. QLSN could potentially be developed as a novel antiplatelet agent.

中文翻译：

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CEACAM1衍生的肽QLSN通过糖蛋白VI损害胶原蛋白诱导的人类血小板活化。

癌胚抗原相关细胞粘附分子1（CEACAM1）通过其胞质免疫受体酪氨酸基抑制基序（ITIM）调节胶原介导的血小板活化。但是，CEACAM1的细胞外裂解片段的功能目前未知。在本研究中，我们使用质谱（MS）鉴定了由基质金属肽酶12（MMP-12）脱落的9个裂解片段，然后合成了具有与该片段相对应的序列的肽。QLSNGNRTLT（QLSN），一种来自CEACAM1 A1结构域的肽，可显着减弱胶原蛋白诱导的血小板聚集。QLSN还减弱了血小板对胶原蛋白的静态粘附。另外，QLSN响应糖蛋白VI（GPVI）选择性激动剂惊厥毒素减少了人体血小板分泌和整联蛋白αIIbβ3的活化。相应地，QLSN治疗显着降低人血小板中惊厥毒素介导的Src，蛋白激酶B（Akt），脾酪氨酸激酶（Syk）和磷脂酶Cγ2（PLCγ2）磷酸化。这些数据表明，CEACAM1衍生的肽QLSN抑制GPVI介导的人血小板活化。QLSN可能被开发为新型抗血小板药。