Vaccinia Virus B1R Kinase Interacts with JIP1 and Modulates c-Jun-Dependent Signaling
Vaccinia Virus B1R Kinase Interacts with JIP1 and Modulates c-Jun-Dependent Signaling
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DOI：
10.1128/jvi.00967-06
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发表时间：
2006-08
影响因子：
5.4
通讯作者：
Claudio R. Santos;S. Blanco;A. Sevilla;P. Lazo
中科院分区：
文献类型：
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作者：
Claudio R. Santos;S. Blanco;A. Sevilla;P. Lazo
摘要 病毒必须适应宿主细胞以保证其生命周期和生存。病毒与宿主细胞相互作用的这一方面可能是由感染早期存在的病毒蛋白（例如丝氨酸-苏氨酸激酶）执行的。痘苗病毒具有早期的 Ser-Thr 激酶 B1R，尽管它是成功病毒感染所必需的，但其对细胞蛋白的影响却知之甚少，因此，其对发病机制的潜在贡献尚不清楚。丝裂原激活蛋白激酶 (MAPK) 的信号传导是由这些激酶与 JIP 支架蛋白之间的复合物组装介导的。为了了解痘苗病毒 B1R 如何影响宿主，研究了其在 MAPK 复合物和 c-Jun 激活的细胞信号传导中的作用。独立于其激酶活性，B1R 可以与 JIP1 支架蛋白的中心区域相互作用。 B1R-JIP1 复合物增加了与 JIP1 结合的 MAPK 量；因此，MKK7和TAK1以更高的亲和力与JIP1结合或更稳定地结合，而与JIP1结合的JNK的磷酸化状态增加。这些更稳定的相互作用的功能结果是响应这些复合物的转录因子（例如 c-Jun）的活性增加。此外，B1R还能够在与JNK靶向的残基不同的残基上直接磷酸化c-Jun，因此，B1R也可以通过独立途径协同激活c-Jun。因此，痘苗病毒 B1R 可以调节响应细胞应激的信号通路。
ABSTRACT Viruses have to adjust to the host cell to guarantee their life cycle and survival. This aspect of the virus-host cell interaction is probably performed by viral proteins, such as serine-threonine kinases, that are present early during infection. Vaccinia virus has an early Ser-Thr kinase, B1R, which, although required for successful viral infection, is poorly characterized regarding its effects on cellular proteins, and thus, its potential contribution to pathogenesis is not known. Signaling by mitogen-activated protein kinase (MAPK) is mediated by the assembly of complexes between these kinases and the JIP scaffold proteins. To understand how vaccinia virus B1R can affect the host, its roles in the cellular signaling by MAPK complexes and c-Jun activation have been studied. Independently of its kinase activity, B1R can interact with the central region of the JIP1 scaffold protein. The B1R-JIP1 complex increases the amount of MAPK bound to JIP1; thus, MKK7 and TAK1 either bind with higher affinity or bind more stably to JIP1, while there is an increase in the phosphorylation state of JNK bound to JIP1. The functional consequence of these more stable interactions is an increase in the activity of transcription factors, such as c-Jun, that respond to these complexes. Furthermore, B1R is also able to directly phosphorylate c-Jun in residues different from those targeted by JNK and, thus, B1R can also cooperate by an independent route in c-Jun activation. Vaccinia virus B1R can thus modulate the signaling of pathways that respond to cellular stress.