加载中…TCR受体通路图
(2020-02-13 21:05:45) | 分类： 积累学习-混杂 |
参考网址：
https://www.cst-c.com.cn/contents/science-cst-pathways-immunology-inflammation/t-cell-receptor-signaling/pathways-tcell
https://cn.sinobiological.com/t-cell-receptor-signaling-pathway.html
T 细胞受体 (TCR) 激活可促进许多信号转导级联反应，通过调控细胞因子产物、细胞生存、增殖和分化来最终决定细胞命运。TCR 激活的早期事件是由淋巴细胞蛋白质酪氨酸激酶 (Lck)，对 TCR/CD3 复合体胞质一侧的免疫受体酪氨酸依赖性活化基序 (ITAMs) 的磷酸化作用。CD45 受体的酪氨酸磷酸酶可调节 Lck 和其他 Src 家族酪氨酸激酶的磷酸化和激活。Zeta 链相关蛋白激酶 (Zap-70) 受到招募，聚集至 TCR/CD3 复合体处并激活，从而启动对下游接头蛋白或骨架蛋白的招募和磷酸化。SLP-76 被 Zap-70 磷酸化后促进招募 Vav (一种鸟苷酸交换因子)、接头蛋白 NCK 和 GADS，以及一种可诱导 T 细胞激酶 (Itk)。磷脂酶 C γ1 (PLCγ1) 被 Itk 磷酸化后导致磷脂酰肌醇-4,5 二磷酸 (PIP2) 的水解，产生第二信使甘油二酯 (DAG) 和三磷酸肌醇
T cell receptors (TCR) play a key role in functioning of T cells and formation of the immunological synapse. It provides connection between T cell and the antigen-presenting cell (APC). TCRs activation promotes a number of signaling cascades that ultimately determine cell fate through regulating cytokine production, cell survival, proliferation, and differentiation. Activation of T lymphocytes is a key event for an efficient response of the immune system.TCR activation is regulated by various co-stimulatory receptors. CD28 provides an essential co-stimulatory signal during T-cell activation, which augments the production of IL-2 (Interleukin-2), increases T-cell proliferation and prevents the induction of anergy and cell death. CD28 ligation by B7-1 or B7-2 helps in bringing the T-Cell and Antigen Presenting Cell membranes into close proximity. Besides CD28, many other transmembrane receptors also modulate specific elements of TCR signaling,such as CD45 and CD4. An early event in TCR activation is phosphorylation of immunoreceptor tyrosine-based activation motifs (ITAMs) on the cytosolic side of the TCR/CD3 complex by lymphocyte protein tyrosine kinase (Lck). The CD45 receptor tyrosine phosphatase modulates the phosphorylation and activation of Lck and other Src family tyrosine kinases. TCR activation also leads to cytoskeletal rearrangements through the activation of GTP-binding proteins Rac and PAK, downstream of ZAP70. Negative regulation of TCR signaling is also significant, in order to keep a check on the hyperactivation of immune response associated with the pathway. SIT (SHP2-interacting transmembrane adaptor protein) is a recently identified transmembrane adaptor protein, which interacts with the SHP2 (SH2-containing protein tyrosine phosphatase-2) via an ITIM (immunoreceptor tyrosine-based inhibition motif), and the complex acts as a critical negative regulator of TCR-mediated signaling. In addition, CTLA4 (cytotoxic T-lymphocyte antigen-4) also negatively regulates T-cell activation. The transmembrane protein CTLA4 also serves as a natural inhibitor. Once T-cells become activated, by whatever disease process is turning them on, the body has a natural process to turn down the T-cell pathways so that it does not get out of control.
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