Institute of Experimental Biomedicine, University Hospital and Rudolf Virchow Center, University of Würzburg, Würzburg, Germany.
PKC Research Consult, 51061 Cologne, Germany.
Cell Signal. 2017 Oct;38:223-229. doi: 10.1016/j.cellsig.2017.07.015. Epub 2017 Jul 21.
Platelet activation at sites of vascular injury is crucial for hemostasis, but it may also cause myocardial infarction or ischemic stroke. Upon platelet activation, cytoskeletal reorganization is essential for platelet secretion and thrombus formation. Members of the protein kinase C family, which includes 12 isoforms, are involved in most platelet responses required for thrombus formation. The atypical protein kinase Cι/λ (PKCι/λ) has been implicated as an important mediator of cell polarity, carcinogenesis and immune cell responses. PKCι/λ is known to be associated with the small GTPase Cdc42, an important mediator of multiple platelet functions; however, its exact function in platelets is not known. To study the role of PKCι/λ, we generated platelet- and megakaryocyte-specific PKCι/λ knockout mice (Prkci) and used them to investigate the function of PKCι/λ in platelet activation and aggregation in vitro and in vivo. Surprisingly, lack of PKCι/λ had no detectable effect on platelet spreading and function in vitro and in vivo under all tested conditions. These results indicate that PKCι/λ is dispensable for Cdc42-triggered processes and for thrombosis and hemostasis in mice.
血小板在血管损伤部位的激活对于止血至关重要，但也可能导致心肌梗死或缺血性中风。在血小板激活时，细胞骨架重排对于血小板分泌和血栓形成是必不可少的。蛋白激酶 C 家族的成员，包括 12 种同工型，参与了血栓形成所需的大多数血小板反应。非典型蛋白激酶 Cι/λ（PKCι/λ）被认为是细胞极性、致癌作用和免疫细胞反应的重要介质。已知 PKCι/λ与小 GTP 酶 Cdc42 相关，Cdc42 是多种血小板功能的重要介质；然而，其在血小板中的确切功能尚不清楚。为了研究 PKCι/λ 的作用，我们生成了血小板和巨核细胞特异性 PKCι/λ 敲除小鼠（Prkci），并利用它们研究 PKCι/λ 在体外和体内血小板激活和聚集中的作用。令人惊讶的是，在所有测试条件下，缺乏 PKCι/λ对血小板在体外和体内的扩展和功能均没有可检测到的影响。这些结果表明，PKCι/λ对于 Cdc42 触发的过程以及在小鼠中的血栓形成和止血是可有可无的。
