The adaptor protein LAT serves as an integration node for signaling pathways that drive T cell activation.
The adaptor protein LAT serves as an integration node for signaling pathways that drive T cell activation.
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DOI：
10.1002/wsbm.1194
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发表时间：
2013-01
影响因子：
7.9
通讯作者：
Houtman, Jon C. D.
中科院分区：
文献类型：
--
作者：
Bartelt, Rebekah R.;Houtman, Jon C. D.
T细胞对病原体的适应性免疫反应至关重要。然而，功能失调的T细胞活性与许多疾病有关，包括器官移植失败、过敏反应、哮喘、自身免疫性疾病和冠状动脉疾病。T细胞对病原体的反应需要诱导主要激活受体，T细胞受体（TCR），以及其他共刺激和粘附受体。这些受体下游激活的信号转导通路驱动免疫反应和疾病进展所需的T细胞反应。我们理解T细胞活化机制的一个关键问题是，来自多个受体的信号通路如何整合在一起，改变T细胞效应物的功能。细胞内信号传导的一个整合节点是T细胞或LAT激活的膜相关接头蛋白连接物。在TCR和其他受体的刺激下，LAT在其细胞质尾部的几个酪氨酸残基上被磷酸化。这导致含有sh2结构域的蛋白及其相关分子的结合，并形成大型多蛋白复合物。这些动态和高度调控的信号复合物促进第二信使的产生，激活下游途径，诱导肌动蛋白细胞骨架聚合，并刺激多种转录因子的活性。因此，来自多个受体的信号通路进入LAT， LAT随后整合这些信息并选择性地诱导对T细胞激活和适应性免疫反应至关重要的通路。
T cells are essential for the adaptive immune response to pathogens. However, dysfunctional T cell activity has been implicated in numerous diseases, including the failure of organ transplants, allergic reactions, asthma, autoimmune disorders, and coronary artery disease. T cell responses to pathogens require the induction of the primary activating receptor, the T cell receptor (TCR), along with other costimulatory and adhesion receptors. Signal transduction pathways activated downstream of these receptors drive T cell responses required for the immune response and disease progression. A key question in our understanding of the mechanism of T cell activation is how signalling pathways emanating from multiple receptors integrate together to alter T cell effector functions. One integration node for intracellular signalling is the membrane-associated adaptor protein linker for the activation of T cells or LAT. Upon stimulation of the TCR and other receptors, LAT is phosphorylated at several tyrosines residues on its cytoplasmic tail. This leads to the binding of SH2-domain containing proteins and their associated molecules and the formation of large multiprotein complexes. These dynamic and highly regulated signalling complexes facilitate the production of second messengers, activate downstream pathways, induce actin cytoskeleton polymerization, and stimulate the activity of multiple transcription factors. Thus, signalling pathways from several receptors feed into LAT, which then integrates this information and selectively induces pathways critical for T cell activation and the adaptive immune response.
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影响因子：
4.4
作者：
Houtman, JCD;Houghtling, RA;Samelson, LE
通讯作者：
Samelson, LE
影响因子：
5.3
作者：
Balagopalan, Lakshmi;Barr, Valarie A.;Samelson, Lawrence E.
通讯作者：
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影响因子：
7.2
作者：
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通讯作者：
Koretzky, Gary A.
影响因子：
64.8
作者：
LI, N;BATZER, A;SCHLESSINGER, J
通讯作者：
SCHLESSINGER, J
影响因子：
11.4
作者：
Barda-Saad, Mira;Shirasu, Naoto;Samelson, Lawrence E.
通讯作者：
Samelson, Lawrence E.