极性蛋白Par1b/EMK/MARK2调节T细胞受体诱导的微管组织中心极化。
The polarity protein Par1b/EMK/MARK2 regulates T cell receptor-induced microtubule-organizing center polarization.
作者信息
Lin Joseph, Hou Kirk K, Piwnica-Worms Helen, Shaw Andrey S
机构信息
Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
出版信息
J Immunol. 2009 Jul 15;183(2):1215-21. doi: 10.4049/jimmunol.0803887. Epub 2009 Jun 24.
Abstract
Engagement of a T cell to an APC induces the formation of an immunological synapse as well as reorientation of the microtubule-organizing center (MTOC) toward the APC. How signals emanating from the TCR induce MTOC polarization is not known. One group of proteins known to play a critical role in asymmetric cell division and cell polarization is the partitioning defective (Par) family of proteins. In this study we found that Par1b, a member of the Par family of proteins, was inducibly phosphorylated following TCR stimulation. This phosphorylation resulted in 14-3-3 protein binding and caused the relocalization of Par1b from the membrane into the cytoplasm. Because a dominant-negative form of Par1b blocked TCR-induced MTOC polarization, our data suggest that Par1b functions in the establishment of T cell polarity following engagement to an APC.
摘要
T细胞与抗原呈递细胞（APC）的结合会诱导免疫突触的形成以及微管组织中心（MTOC）向APC的重新定向。TCR发出的信号如何诱导MTOC极化尚不清楚。已知在不对称细胞分裂和细胞极化中起关键作用的一组蛋白质是Par（partitioning defective）家族蛋白质。在本研究中，我们发现Par家族蛋白质成员Par1b在TCR刺激后可被诱导磷酸化。这种磷酸化导致14-3-3蛋白结合，并使Par1b从细胞膜重新定位到细胞质中。由于Par1b的显性负性形式阻断了TCR诱导的MTOC极化，我们的数据表明Par1b在T细胞与APC结合后的极性建立中发挥作用。
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本文引用的文献
1
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Proc Natl Acad Sci U S A. 2008 Nov 25;105(47):18378-83. doi: 10.1073/pnas.0809661105. Epub 2008 Nov 14.
2
Dishevelled-induced phosphorylation regulates membrane localization of Par1b.蓬乱蛋白诱导的磷酸化调节Par1b的膜定位。
Biochem Biophys Res Commun. 2008 Oct 31;375(4):660-5. doi: 10.1016/j.bbrc.2008.08.098. Epub 2008 Aug 28.
3
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J Neurosci. 2008 May 28;28(22):5710-20. doi: 10.1523/JNEUROSCI.0911-08.2008.
4
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5
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Mol Immunol. 2008 Jan;45(1):117-26. doi: 10.1016/j.molimm.2007.05.003. Epub 2007 Jun 22.
6
Asymmetric T lymphocyte division in the initiation of adaptive immune responses.适应性免疫反应启动过程中的不对称T淋巴细胞分裂
Science. 2007 Mar 23;315(5819):1687-91. doi: 10.1126/science.1139393. Epub 2007 Mar 1.
7
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8
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