Tyrosine kinases and phosphatases in cell cycle checkpoint responses

细胞周期检查点反应中的酪氨酸激酶和磷酸酶

• 批准号: nhmrc : 436602
• 负责人: Prof Tony Tiganis
• 金额: $ 34.27万
• 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/tyrosine-kinases-phosphatases-checkpoint-responses/76203
• 关键词: Tyrosine; kinases; phosphatases; cell; cycle

In order for an organism to grow and develop, the cells that make up the tissues and organs need to undergo a process of cellular division, wherein individual cells grow and then divide into two cells. During this process of cellular growth and division the entire genome needs to be duplicated (this occurs during S-phase) and then divided equally into the two daughter cells. In S-phase several so-called 'checkpoint' mechanisms exist which ensure that this occurs in an orderly and precise manner. The so-called 'DNA replication checkpoint' delays S-phase progression in response to 'replication stresses' that may otherwise cause DNA damage. Protein tyrosine kinases (PTKs) are hyperactivated in many human solid tumours and blood malignancies contributing to varied aspects of tumour progression. Our preliminary studies indicate that the inactivation of PTKs by protein tyrosine phosphatases may be essential for the suppression of S-phase progression in response to replication stress. Our goal is to understand the molecular mechanisms by which PTKs and tyrosine phosphatases contribute to S-phase checkpoints. Our studies will provide important insights into DNA replication stress-induced checkpoint responses in mammals and identify unprecedented mechanisms by which hyperactivated PTKs may contribute to tumour development.

为了使生物体生长和发育，构成组织和器官的细胞需要经历细胞分裂的过程，其中单个细胞生长然后分裂成两个细胞。在细胞生长和分裂的过程中，整个基因组需要复制（这发生在 S 期），然后平均分为两个子细胞。在 S 阶段，存在一些所谓的“检查点”机制，可确保这一过程以有序且精确的方式发生。所谓的“DNA 复制检查点”会延迟 S 期进程，以应对“复制压力”，否则可能会导致 DNA 损伤。蛋白酪氨酸激酶 (PTK) 在许多人类实体瘤和血液恶性肿瘤中过度激活，导致肿瘤进展的各个方面。我们的初步研究表明，蛋白酪氨酸磷酸酶使 PTK 失活可能对于抑制复制应激引起的 S 期进展至关重要。我们的目标是了解 PTK 和酪氨酸磷酸酶促成 S 期检查点的分子机制。我们的研究将为哺乳动物中 DNA 复制应激诱导的检查点反应提供重要见解，并确定过度激活的 PTK 可能促进肿瘤发展的前所未有的机制。