Blood:Csk和磷酸酶CD148具有维持血小板稳态的作用

2018-02-11 MedSci MedSci原创

Src家族激酶(SFKs)协调血小板的信号激活和扩散,但目前尚不清楚其如何调控。本研究中,研究人员发现敲除小鼠的Src激酶(Csk)的C末端和受体样蛋白酪氨酸-磷酸酶CD148可导致血小板SFK活性增强,证明上述蛋白对调节血小板反应至关重要。与此相矛盾的,Csk/CD148-缺陷小鼠却表现为血栓形成减少、受伤后出血增加,而不是血栓形成的表现。该现象涉及一个多重负反馈调节机制,包括下调以免疫受体酪氨

Src家族激酶(SFKs)协调血小板的信号激活和扩散,但目前尚不清楚其如何调控。本研究中,研究人员发现敲除小鼠的Src激酶(Csk)的C末端和受体样蛋白酪氨酸-磷酸酶CD148可导致血小板SFK活性增强,证明上述蛋白对调节血小板反应至关重要。

与此相矛盾的,Csk/CD148-缺陷小鼠却表现为血栓形成减少、受伤后出血增加,而不是血栓形成的表现。该现象涉及一个多重负反馈调节机制,包括下调以免疫受体酪氨酸为基础的激活模体(ITAM)和包含ITAM单体的GPVI-FcR受体的γ链和CLEC-2,上调包含受体G6b-B的免疫受体酪氨酸为基础的抑制模体(ITIM)及与其相互作用的酪氨酸磷酸酶Shp1和Shp2。

本研究证明了SFKs在激活ITIM信号中的非常规作用;Csk和CD148是调控血栓形成和血小板稳定能力的关键分子,揭示了细胞内抑制病理性血栓形成的固有机制。

原始出处:

Jun Mori,et al.Maintenance of murine platelet homeostasis by the kinase Csk and the phosphatase CD148.Blood  2018  :blood-2017-02-768077;  doi: https://doi.org/10.1182/blood-2017-02-768077

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    2018-02-24 一叶知秋
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    2018-10-28 changfy
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    2019-01-07 FukaiBao
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    2018-02-13 jihuaijun1112

    学习学习学习

    0

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    2018-02-12 衣带渐宽

    学习

    0

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    2018-02-12 周周人

    学习.

    0

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    2018-02-11 清风拂面

    谢谢分享学习

    0

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    2018-02-11 zdvfsadb

    学习了

    0