STAT3-Stathmin Interactions Control Microtubule Dynamics in Migrating T-cells
STAT3-Stathmin Interactions Control Microtubule Dynamics in Migrating T-cells
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DOI：
10.1074/jbc.m807761200
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发表时间：
2009-05-01
影响因子：
4.8
通讯作者：
Volkov, Yuri
中科院分区：
文献类型：
--
作者：
Verma, Navin K.;Dourlat, Jennifer;Volkov, Yuri
T细胞迁移是一个复杂的高度协调的过程，涉及细胞粘附到高内皮微静脉或细胞外基质的表面受体/配体相互作用，细胞骨架重排，和磷酸化依赖性信号级联。调节T细胞迁移的机制对于理解各种疾病的发病机制具有相当大的相关性，例如慢性炎性疾病和癌症转移。本研究旨在确定潜在的参与STAT 3，一种潜在的转录因子，介导整合素诱导的T细胞迁移。使用我们先前表征的淋巴细胞迁移的体外模型，我们证明了在通过LFA-1触发的Hut 78 T淋巴瘤细胞的主动运动过程中，STAT 3被激活并易位到细胞核。通过多种方法阻断STAT 3信号传导抑制了LFA 1通过微管的不稳定和微管蛋白的翻译后修饰诱导的T细胞运动。在这里，我们表明STAT 3与stathmin物理相互作用，以调节迁移T细胞中的微管动力学。这些观察结果强烈表明STAT 3对于T细胞迁移和相关信号传导事件至关重要。
T-cell migration is a complex highly coordinated process that involves cell adhesion to the high endothelial venules or to the extracellular matrix by surface receptor/ligand interactions, cytoskeletal rearrangements, and phosphorylation-dependent signaling cascades. The mechanism(s) that regulates T-cell migration is of considerable relevance for understanding the pathogenesis of various diseases, such as chronic inflammatory diseases and cancer metastasis. This study was designed to identify potential involvement of STAT3, a latent transcription factor, in mediating integrin-induced T-cell migration. Using our previously characterized in vitro model for lymphocyte migration, we demonstrate that STAT3 is activated and translocated to the nucleus during the process of active motility of Hut78 T-lymphoma cells triggered via LFA-1. Blocking STAT3 signaling by multiple approaches inhibitedLFA1- induced T-cell locomotion via destabilization of microtubules and post-translational modification of tubulin. Here, we show that STAT3 physically interacts with stathmin to regulate microtubule dynamics in migrating T-cells. These observations strongly indicate that STAT3 is critically important for T-cell migration and associated signaling events.