免疫受体信号传导中的 Src 家族激酶 Lyn,Endocrinology

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免疫受体信号传导中的 Src 家族激酶 Lyn
Endocrinology ( IF 3.8 ) Pub Date : 2021-07-28 , DOI: 10.1210/endocr/bqab152
Ben F Brian ₁ , Tanya S Freedman _{1,

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Affiliation

免疫细胞激活的有效调节对于确保免疫反应和为消除病原体而产生的炎症在空间和时间上受到限制以限制组织损伤至关重要。当免疫受体信号失调导致无节制的炎症和器官损伤时，就会发生自身免疫性疾病。相反，肿瘤可以利用造血细胞的组织愈合和免疫抑制功能来促进转移和逃避治疗。Src 家族激酶 Lyn 是免疫受体信号传导的重要调节因子，在骨髓免疫细胞（例如中性粒细胞、树突细胞、单核细胞、巨噬细胞）和 B 淋巴细胞中启动促炎和抑制信号通路。Lyn 信号缺陷与自身免疫性疾病有关，但 Lyn、与一系列其他 Src 家族激酶一起表达，可能独特地指导正信号和负信号仍然不完全定义。这篇综述描述了我们目前对 Lyn 对免疫受体信号传导的激活和抑制作用的理解，以及这些过程如何促进骨髓和 B 细胞功能。我们还强调了最近的研究表明，通过选择性剪接产生的两种蛋白质lyn、LynA 和 LynB 差异调节免疫和癌细胞信号传导。这些原则也可以扩展到其他表达 Lyn 的细胞，例如神经元和内分泌细胞。揭示 Lyn 功能的共同和细胞特异性方面可能会导致新的方法来治疗从自身免疫和神经生成疾病到癌症的病理学中失调的通路。

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The Src-family kinase Lyn in immunoreceptor signaling

Effective regulation of immune-cell activation is critical for ensuring that the immune response, and inflammation generated for the purpose of pathogen elimination, is limited in space and time to limit tissue damage. Autoimmune disease can occur when immunoreceptor signaling is dysregulated, leading to unrestrained inflammation and organ damage. Conversely, tumors can coopt the tissue-healing and immunosuppressive functions of hematopoietic cells to promote metastasis and evade therapy. The Src-family kinase Lyn is an essential regulator of immunoreceptor signaling, initiating both pro-inflammatory and suppressive signaling pathways in myeloid immune cells (e.g. neutrophils, dendritic cells, monocytes, macrophages) and in B lymphocytes. Defects in Lyn signaling are implicated in autoimmune disease, but mechanisms by which Lyn, expressed along with a battery of other Src-family kinases, may uniquely direct both positive and negative signaling remain incompletely defined. This review describes our current understanding of the activating and inhibitory contributions of Lyn to immunoreceptor signaling and how these processes contribute to myeloid and B-cell function. We also highlight recent work suggesting that the two proteins generated by alternative splicing of lyn, LynA and LynB, differentially regulate immune and cancer-cell signaling. These principles may also extend to other Lyn-expressing cells, such as neuronal and endocrine cells. Unraveling the common and cell-specific aspects of Lyn function could lead to new approaches to therapeutically targeting dysregulated pathways in pathologies from autoimmune and neurogenerative disease to cancer.

更新日期：2021-08-01

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