Differently phosphorylated forms of the cortactin homolog HS1 mediate distinct functions in natural killer cells
Differently phosphorylated forms of the cortactin homolog HS1 mediate distinct functions in natural killer cells
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DOI：
10.1038/ni.1630
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发表时间：
2008-08-01
影响因子：
30.5
通讯作者：
Cooper, John A.
中科院分区：
文献类型：
--
作者：
Butler, Boyd;Kastendieck, Diana H.;Cooper, John A.
在这里，我们研究了 HS1（皮质蛋白的造血细胞特异性同源物）在自然杀伤细胞基于肌动蛋白的功能中的参与情况。 HS1 参与 T 细胞调节已被证实，因为 HS1 是免疫突触形成所必需的。自然杀伤细胞中 HS1 的“敲除”导致靶细胞裂解、细胞粘附、趋化性和裂解突触处肌动蛋白组装的缺陷。 397 位酪氨酸残基 (Tyr397) 的磷酸化是粘附整合素配体 ICAM-1 和细胞溶解所必需的，而 Tyr378 的磷酸化是趋化性所必需的。 Tyr397 的磷酸化也是整合素信号转导和整合素、接头和肌动蛋白向裂解突触的募集所必需的。因此，HS1 对于自然杀伤细胞中的信号传导和肌动蛋白组装至关重要，并且两个磷酸化酪氨酸残基的功能是不同且可分离的。
Here we investigated the involvement of HS1, the hematopoietic cell-specific homolog of cortactin, in the actin-based functions of natural killer cells. Involvement of HS1 in T cell regulation has been established, as HS1 is required for the formation of immune synapses. 'Knockdown' of HS1 in natural killer cells resulted in defective lysis of target cells, cell adhesion, chemotaxis and actin assembly at the lytic synapse. Phosphorylation of the tyrosine residue at position 397 (Tyr397) was required for adhesion to the integrin ligand ICAM-1 and for cytolysis, whereas phosphorylation of Tyr378 was required for chemotaxis. Phosphorylation of Tyr397 was also required for integrin signaling and recruitment of integrins, adaptors and actin to the lytic synapse. Thus, HS1 is essential for signaling and actin assembly in natural killer cells, and the functions of the two phosphorylated tyrosine residues are distinct and separable.