A signaling network stimulated by β2 integrin promotes the polarization of lytic granules in cytotoxic cells.
A signaling network stimulated by β2 integrin promotes the polarization of lytic granules in cytotoxic cells.
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DOI：
10.1126/scisignal.2005629
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发表时间：
2014-10-07
影响因子：
7.3
通讯作者：
Long EO
中科院分区：
文献类型：
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作者：
Zhang M;March ME;Lane WS;Long EO
细胞毒淋巴细胞技能通过极化靶细胞释放内含穿孔素的颗粒。在自然杀伤细胞中，β2整联蛋白与其配体ICAM-1的结合不仅足以促进粘附，还足以促进溶解颗粒极化。这提供了一个独特的机会来研究在不存在脱粒的情况下的极化，以及独立于来自其他受体的由内而外信号的β2整联蛋白信号传导。使用无偏见的蛋白质组学方法，我们确定了一个信号网络集中在一个整合素连接的激酶（ILK）-Pyk 2-桩蛋白核心，所需的颗粒极化。在ILK下游，控制细胞极性的高度保守的Cdc 42-Par 6信号通路被激活，并且是颗粒极化所必需的。这些结果描绘了单独β2整合素结合诱导的两个连接的信号网络，其被整合以控制微管组织中心和相关的裂解颗粒在细胞毒性期间朝向与靶细胞接触的位点的极化。
Cytotoxic lymphocyte skill target cells by polarized release of the content of perforin-containing granules. In natural killer cells, the binding of β2 integrin to its ligand ICAM-1 is sufficient to promote not only adhesion but also lytic granule polarization. This provided a unique opportunity to study polarization in the absence of degranulation, and β2 integrin signaling independently of inside-out signals from other receptors. Using an unbiased proteomics approach we identified a signaling network centered on an integrin-linked kinase (ILK)–Pyk2–Paxillin core that was required for granule polarization. Downstream of ILK, the highly conserved Cdc42–Par6 signaling pathway that controls cell polarity was activated and required for granule polarization. These results delineate two connected signaling networks induced upon β2 integrin engagement alone, which are integrated to control polarization of the microtubule organizing center and associated lytic granules toward the site of contact with target cells during cellular cytotoxicity.
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影响因子：
64.5
作者：
Fukata, M;Watanabe, T;Kaibuchi, K
通讯作者：
Kaibuchi, K
影响因子：
20.3
作者：
Cheng, Shuhua;Coffey, Greg;Wang, Y. Lynn
通讯作者：
Wang, Y. Lynn
影响因子：
4.4
作者：
Barber, DF;Long, EO
通讯作者：
Long, EO
DOI：
10.1073/pnas.0604206103
发表时间：
2006-07-11
影响因子：
11.1
作者：
Hadjihannas, Michel V.;Brueckner, Martina;Behrens, Juergen
通讯作者：
Behrens, Juergen
影响因子：
21.3
作者：
通讯作者：
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