Abl collaborates with Src family kinases to stimulate actin-based motility of vaccinia virus
Abl collaborates with Src family kinases to stimulate actin-based motility of vaccinia virus
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DOI：
10.1111/j.1462-5822.2005.00613.x
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发表时间：
2006-02-01
影响因子：
3.4
通讯作者：
Way, M
中科院分区：
文献类型：
--
作者：
Newsome, TP;Weisswange, I;Way, M
细胞外牛痘病毒在质膜上局部激活Src导致信号级联反应，其作用是刺激病毒下方的肌动蛋白聚合，以增强其细胞到细胞的传播。这种信号级联的启动涉及Src介导的病毒膜蛋白A36 R的酪氨酸112和132的磷酸化。在这里，我们表明，招聘Src是依赖于其豆蔻酰化和相互作用与A36 R上游的酪氨酸112和132。我们进一步表明，Src，Fyn和Yes对这些酪氨酸残基具有独特的特异性。使用缺乏Src，Fyn和Yes的细胞系，我们证明了多个Src家族成员可以刺激牛痘诱导的肌动蛋白聚合，也揭示了Abl家族激酶的作用。此外，Abl和Arg能够在体外磷酸化A36 R，并被募集到牛痘诱导的肌动蛋白尾部。多个酪氨酸激酶家族直接磷酸化A36R的能力确保了在各种细胞条件下将发生牛痘病毒的稳健的细胞间传播。
Local activation of Src at the plasma membrane by extracellular vaccinia virus results in a signalling cascade that acts to stimulate actin polymerization beneath the virus to enhance its cell-to-cell spread. Initiation of this signalling cascade involves Src-mediated phosphorylation of tyrosine 112 and 132 of the viral membrane protein A36R. Here we show that recruitment of Src is dependent on its myristoylation and an interaction with A36R upstream of tyrosine 112 and 132. We further show that Src, Fyn and Yes have unique specificities towards these tyrosine residues. Using cell lines deficient in Src, Fyn and Yes, we demonstrate that multiple Src family members can stimulate vaccinia-induced actin polymerization and also uncover a role for Abl family kinases. Additionally, Abl and Arg are able to phosphorylate A36R in vitro and are recruited to vaccinia-induced actin tails. The ability of multiple families of tyrosine kinases to directly phosphorylate A36R ensures robust cell-to-cell spread of vaccinia virus will occur under a variety of cellular conditions.