The role of protein tyrosine phosphatases regulating Eph RTK-signalling and modulating invasive tumour cell properties.

蛋白酪氨酸磷酸酶调节 Eph RTK 信号传导和调节侵袭性肿瘤细胞特性的作用。

• 批准号: nhmrc : 436774
• 负责人: A/Pr Martin Lackmann
• 金额: $ 20.26万
• 依托单位: Monash University
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2007
• 资助国家: 澳大利亚
• 起止时间: 2007-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/role-protein-tyrosine-cell-properties/100530
• 关键词: role; protein; tyrosine; phosphatases; regulating

The Ephs and interacting ephrins are proteins on the cell surface, which enable orientation of cells that move within the body tissues and organs, but also in tumours. Eph proteins have tyrosine kinase enzyme activity that becomes active after binding ephrins on neighbouring cells. Once active, they instruct these cells to change their shape and their adhesion to the substratum or between each other, and to become more motile. In adult organisms Ephs and ephrins are low in most cells, but they re-appear in many tumors. For example, when normal cells in the skin (melanocytes) become tumor cells, they often will have Ephs and ephrins on their surface. It is believed that these proteins will now affect if these melanoma cells will migrate and to which locations within the body. In our studies we will examine what controls the activity of Eph proteins. In particular, a class of enzymes called tyrosine phosphatases are known to regulate the function of tyrosine kinase receptors, however it is not clear which particular phosphatase regulates EphA3, the focus of our studies. We will find out, which set of phosphatases regulates EphA3 function and whether exposure to oxidative conditions, such as UV radiation, also activates Ephs and instructs tumour cells to become more motile and to invade other areas of the body. The understanding of this mechanism will help to understand the cause of cancers such as melanoma and might offer possibilities to optimise new strategies for its treatment.

Ephs 和相互作用的肝配蛋白是细胞表面的蛋白质，它们使细胞在身体组织和器官内以及肿瘤内移动时能够定向。 Eph 蛋白具有酪氨酸激酶活性，在与邻近细胞上的肝配蛋白结合后变得活跃。一旦活跃，它们就会指示这些细胞改变它们的形状以及它们与基质或彼此之间的粘附，并变得更加活跃。在成体生物体中，大多数细胞中的 Ephs 和肝配蛋白含量较低，但它们会在许多肿瘤中重新出现。例如，当皮肤中的正常细胞（黑色素细胞）变成肿瘤细胞时，它们的表面通常会含有Ephs和ephrins。据信，这些蛋白质现在将影响这些黑色素瘤细胞是否会迁移以及迁移到体内的哪些位置。在我们的研究中，我们将研究控制 Eph 蛋白活性的因素。特别是，已知一类称为酪氨酸磷酸酶的酶可调节酪氨酸激酶受体的功能，但尚不清楚哪种特定磷酸酶调节我们研究的重点 EphA3。我们将找出哪组磷酸酶调节 EphA3 功能，以及暴露于氧化条件（例如紫外线辐射）是否也会激活 Ephs 并指示肿瘤细胞变得更加活跃并侵入身体的其他区域。了解这种机制将有助于了解黑色素瘤等癌症的病因，并可能为优化其治疗新策略提供可能性。