Syk Is Recruited to Stress Granules and Promotes Their Clearance through Autophagy
Syk Is Recruited to Stress Granules and Promotes Their Clearance through Autophagy
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DOI：
10.1074/jbc.m115.642900
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发表时间：
2015-11-13
影响因子：
4.8
通讯作者：
Geahlen, Robert L.
中科院分区：
文献类型：
--
作者：
Krisenko, Mariya O.;Higgins, Renee L.;Geahlen, Robert L.
Syk是一种细胞质激酶，在免疫系统中发挥多种功能，将抗原和抗原抗体复合物的受体偶联至适应性和先天性免疫应答。最近的研究已经确定了激酶在癌细胞中的其他作用，其表达可以促进或抑制肿瘤细胞生长，这取决于背景。Syk结合蛋白的蛋白质组学分析确定了几个相互作用的合作伙伴也被发现招募到应力颗粒。我们在这里表明，处理细胞与诱导剂的压力颗粒形成导致招聘Syk这些蛋白质-RNA复合物。这种募集需要酪氨酸上Syk的磷酸化，并导致应激颗粒处或附近蛋白质的磷酸化。Grb 7被鉴定为参与Syk向应激颗粒的募集的Syk结合蛋白。这种募集促进自噬体的形成，并在压力缓解后从细胞中清除压力颗粒，从而增强细胞在压力刺激下存活的能力。
Syk is a cytoplasmic kinase that serves multiple functions within the immune system to couple receptors for antigens and antigen-antibody complexes to adaptive and innate immune responses. Recent studies have identified additional roles for the kinase in cancer cells, where its expression can either promote or suppress tumor cell growth, depending on the context. Proteomic analyses of Syk-binding proteins identified several interacting partners also found to be recruited to stress granules. We show here that the treatment of cells with inducers of stress granule formation leads to the recruitment of Syk to these protein-RNA complexes. This recruitment requires the phosphorylation of Syk on tyrosine and results in the phosphorylation of proteins at or near the stress granule. Grb7 is identified as a Syk-binding protein involved in the recruitment of Syk to the stress granule. This recruitment promotes the formation of autophagosomes and the clearance of stress granules from the cell once the stress is relieved, enhancing the ability of cells to survive the stress stimulus.