EphrinB1 signals from the cell surface to the nucleus by recruitment of STAT3
EphrinB1 signals from the cell surface to the nucleus by recruitment of STAT3
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DOI：
10.1073/pnas.0702337104
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发表时间：
2007-10-30
影响因子：
11.1
通讯作者：
Daar, Ira O.
中科院分区：
文献类型：
--
作者：
Bong, Yong-Sik;Lee, Hyun-Shik;Daar, Ira O.
受体酪氨酸激酶的Eph（促红细胞生成素产生的肝癌）家族及其膜结合配体——肝配蛋白，通过介导细胞间信号传导事件参与调节发育过程中的细胞黏附和迁移。跨膜肝配蛋白B（Eph受体相互作用蛋白B）是一种双向信号分子，它通过激活位于另一个细胞上的同源受体酪氨酸激酶发出正向信号。反向信号可通过其保守的C末端胞质结构域的酪氨酸磷酸化转导到表达肝配蛋白B的细胞中。尽管对于肝配蛋白B如何发出影响细胞骨架成分的信号已有一些了解，但对于肝配蛋白B1反向信号如何影响转录过程知之甚少。在此我们报道，信号转导和转录激活因子3（STAT3）能够以磷酸化依赖的方式与肝配蛋白B1相互作用，从而导致STAT3转录活性增强。这种活性依赖于酪氨酸激酶Jak2，并且肝配蛋白B1胞内结构域中的两个酪氨酸对于与STAT3的结合及其激活至关重要。STAT3被募集到肝配蛋白B1，以及由此产生的依赖于Jak2的激活和报告基因靶标的转录，揭示了从肝配蛋白B1到细胞核的一条信号通路。
The Eph (erythropoietin-producing hepatoma) family of receptor tyrosine kinases and their membrane-bound ligands, the ephrins, have been implicated in regulating cell adhesion and migration during development by mediating cell-to-cell signaling events. The transmembrane ephrinB (Eph receptor interactor B) protein is a bidirectional signaling molecule that sends a forward signal through the activation of its cognate receptor tyrosine kinase, residing on another cell. A reverse signal can be transduced into the ephrinB expressing cell via tyrosine phosphorylation of its conserved C-terminal cytoplasmic domain. Although some insight has been gained regarding how ephrinB may send signals affecting cytoskeletal components, little is known about how ephrinBl reverse signaling affects transcriptional processes. Here we report that signal transducer and activator of transcription 3 (STAT3) can interact with ephrinB1 in a phosphorylation-dependent manner that leads to enhanced activation of STAT3 transcriptional activity. This activity depends on the tyrosine kinase Jak2, and two tyrosines within the intracellular domain of ephrinB1 are critical for the association with STAT3 and its activation. The recruitment of STAT3 to ephrinBl, and its resulting Jak2-dependent activation and transcription of reporter targets, reveals a signaling pathway from ephrinBl to the nucleus.