Cell Signalling Group, Laboratory for Cancer Medicine, Western Australian Institute for Medical Research, Centre for Medical Research, The University of Western Australia, Rear 50 Murray Street, Perth, WA, 6000, Australia.
Cell Commun Signal. 2012 Jul 17;10(1):21. doi: 10.1186/1478-811X-10-21.
Src family kinases such as Lyn are important signaling intermediaries, relaying and modulating different inputs to regulate various outputs, such as proliferation, differentiation, apoptosis, migration and metabolism. Intriguingly, Lyn can mediate both positive and negative signaling processes within the same or different cellular contexts. This duality is exemplified by the B-cell defect in Lyn-/- mice in which Lyn is essential for negative regulation of the B-cell receptor; conversely, B-cells expressing a dominant active mutant of Lyn (Lynup/up) have elevated activities of positive regulators of the B-cell receptor due to this hyperactive kinase. Lyn has well-established functions in most haematopoietic cells, viz. progenitors via influencing c-kit signaling, through to mature cell receptor/integrin signaling, e.g. erythrocytes, platelets, mast cells and macrophages. Consequently, there is an important role for this kinase in regulating hematopoietic abnormalities. Lyn is an important regulator of autoimmune diseases such as asthma and psoriasis, due to its profound ability to influence immune cell signaling. Lyn has also been found to be important for maintaining the leukemic phenotype of many different liquid cancers including acute myeloid leukaemia (AML), chronic myeloid leukaemia (CML) and B-cell lymphocytic leukaemia (BCLL). Lyn is also expressed in some solid tumors and here too it is establishing itself as a potential therapeutic target for prostate, glioblastoma, colon and more aggressive subtypes of breast cancer. LAY To relay information, a cell uses enzymes that put molecular markers on specific proteins so they interact with other proteins or move to specific parts of the cell to have particular functions. A protein called Lyn is one of these enzymes that regulate information transfer within cells to modulate cell growth, survival and movement. Depending on which type of cell and the source of the information input, Lyn can positively or negatively regulate the information output. This ability of Lyn to be able to both turn on and turn off the relay of information inside cells makes it difficult to fully understand its precise function in each specific circumstance. Lyn has important functions for cells involved in blood development, including different while blood cells as well as red blood cells, and in particular for the immune cells that produce antibodies (B-cells), as exemplified by the major B-cell abnormalities that mice with mutations in the Lyn gene display. Certain types of leukaemia and lymphoma appear to have too much Lyn activity that in part causes the characteristics of these diseases, suggesting it may be a good target to develop new anti-leukaemia drugs. Furthermore, some specific types, and even specific subtypes, of solid cancers, e.g. prostate, brain and breast cancer can also have abnormal regulation of Lyn. Consequently, targeting this protein in these cancers could also prove to be beneficial.
Src 家族激酶（如 Lyn）是重要的信号转导中介，传递和调节不同的输入以调节各种输出，如增殖、分化、凋亡、迁移和代谢。有趣的是，Lyn 可以在同一或不同的细胞环境中调节正向和负向信号过程。这种双重性的一个例子是 Lyn-/- 小鼠中的 B 细胞缺陷，其中 Lyn 对于 B 细胞受体的负调节是必不可少的；相反，表达 Lyn 显性激活突变体（Lynup/up）的 B 细胞由于这种高活性激酶而具有 B 细胞受体的正调节因子的升高活性。Lyn 在大多数造血细胞中具有既定的功能，例如通过影响 c-kit 信号来影响祖细胞，直至成熟细胞受体/整合素信号，例如红细胞、血小板、肥大细胞和巨噬细胞。因此，这种激酶在调节造血异常方面具有重要作用。由于其对免疫细胞信号的深远影响，Lyn 是哮喘和牛皮癣等自身免疫性疾病的重要调节剂。Lyn 还被发现对于维持许多不同的液体癌（包括急性髓性白血病 (AML)、慢性髓性白血病 (CML) 和 B 细胞淋巴细胞白血病 (BCLL)）的白血病表型很重要。Lyn 也在一些实体瘤中表达，在这里它也被确立为前列腺、胶质母细胞瘤、结肠和更具侵袭性的乳腺癌亚型的潜在治疗靶点。
Lay 为了传递信息，细胞使用在特定蛋白质上添加分子标记的酶，以便它们与其他蛋白质相互作用或移动到细胞的特定部分以发挥特定功能。一种称为 Lyn 的蛋白质就是调节细胞内信息传递以调节细胞生长、存活和运动的酶之一。根据细胞类型和信息输入的来源，Lyn 可以正向或负向调节信息输出。Lyn 能够打开和关闭细胞内信息传递的这种能力使得难以完全理解其在每种特定情况下的精确功能。Lyn 对参与血液发育的细胞具有重要功能，包括不同的白细胞和红细胞，特别是对于产生抗体的免疫细胞（B 细胞），这从 Lyn 基因突变小鼠显示的主要 B 细胞异常中可见一斑。某些类型的白血病和淋巴瘤似乎具有过多的 Lyn 活性，这部分导致了这些疾病的特征，表明它可能是开发新的抗白血病药物的良好靶点。此外，某些特定类型甚至特定亚型的实体癌，例如前列腺癌、脑癌和乳腺癌，也可能存在 Lyn 的异常调节。因此，针对这些癌症中的这种蛋白质也可能被证明是有益的。
