Regulation of TNF and SFK signalling in immune cells by TCPTP

TCPTP 对免疫细胞中 TNF 和 SFK 信号传导的调节

• 批准号: nhmrc : 384147
• 负责人: Prof Tony Tiganis
• 金额: $ 30.27万
• 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: 2006
• 资助国家: 澳大利亚
• 起止时间: 2006-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/regulation-tnf-sfk-cells-tcptp/98407
• 关键词: Regulation; TNF; SFK; signalling; immune

Tumour necrosis factor (TNF) is a potent proinflammatory cytokine that plays an important role in immunity and inflammation. TNF acts on the cell surface to activate two key cellular communication or signalling pathways: the mitogen-activated protein kinase (MAPK) pathway and the nuclear factor kappaB (NFkappaB) pathway. The relative activation of the two pathways can dictate whether cells live and proliferate or differentiate or otherwise die in response to TNF, and therefore determine the nature of the immune or inflammatory response. The T-cell protein tyrosine phosphatase (TCPTP) is known to be important in the immune system and serves as a negative regulator of inflammation. Our preliminary studies have identified TCPTP as a selective regulator of TNF-induced MAPK but not NFkappaB signaling. TCPTP exerts its effects by inactivating Src family kinases (SFK) which are themselves integral to immune and inflammatory responses. In this proposal we will elucidate the molecular basis for TCPTP function in TNF- signalling and characterise the role of TCPTP in TNF and SFK functions in immune cells, in particular T-cells.

肿瘤坏死因子（TNF）是一种有效的促炎细胞因子，在免疫和炎症中发挥重要作用。 TNF 作用于细胞表面，激活两条关键的细胞通讯或信号传导途径：丝裂原激活蛋白激酶 (MAPK) 途径和核因子 kappaB (NFkappaB) 途径。两条通路的相对激活可以决定细胞是否存活、增殖或分化或以其他方式死亡以响应 TNF，从而决定免疫或炎症反应的性质。 T 细胞蛋白酪氨酸磷酸酶 (TCPTP) 已知在免疫系统中很重要，并且是炎症的负调节因子。我们的初步研究已确定 TCPTP 是 TNF 诱导的 MAPK 而非 NFkappaB 信号传导的选择性调节剂。 TCPTP 通过灭活 Src 家族激酶 (SFK) 发挥作用，而 Src 家族激酶本身是免疫和炎症反应不可或缺的一部分。在本提案中，我们将阐明 TCPTP 在 TNF 信号传导中的分子基础，并描述 TCPTP 在免疫细胞（特别是 T 细胞）中 TNF 和 SFK 功能中的作用。