The role of glycosylation in receptor activation

糖基化在受体激活中的作用

• 批准号: 203498-2013
• 负责人: Szewczuk, Myron
• 金额: $ 2.19万
• 依托单位: Queen's University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2013
• 资助国家: 加拿大
• 起止时间: 2013-01-01 至 2014-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=523469
• 关键词: role; glycosylation; receptor; activation

The nature of our research program is to study the role of sugar residues expressed by many proteins and receptors in cellular activation. These sugar residues carry out functions essential for the maintenance of biological activities of cells, including transmission of biological information between cell membrane surfaces, formation of cell morphology and maintenance of complicated physiological cell responses to stimuli. In particular, our research focuses on the receptor tyrosine kinases (RTKs) which are the cell surface receptors for many polypeptide growth factors, cytokines and hormones used by our body for normal survival. In addition, we have included the mammalian Toll-like receptors (TLRs) which are a family of receptors that recognize pathogen-associated molecular patterns. Thus, it is critical that the intensity and duration of these receptor responses to stimuli must be tightly controlled. Various reports have suggested that receptor sugar modification may in fact be the invisible link connecting receptor binding, activation and cellular responses. My HQP trainees have identified the key players linked in the hormone-induced receptor activation process(es). Neu1 sialidase was uncovered as an essential enzyme which acts through a common receptor level signaling pathway on the cell surface to regulate the activation of a number of these receptors. Although the precise relationship between Neu1 and receptor activation has yet to be fully elucidated, it represents a new or pioneering approach to cell regulation pathways that have been missed in the field. If successful, the findings would be highly significant to the entire field of receptor-mediated cellular biology. The finding that receptor sugar modifications is critical for normal cell activation has immense potential for use as research tools for HQP trainees or even in therapeutic regulation of receptor bioactivity and downstream cell physiology.

我们研究计划的性质是研究许多蛋白质和受体表达的糖残基在细胞活化中的作用。这些糖残基执行维持细胞生物活性所必需的功能，包括在细胞膜表面之间传递生物信息、形成细胞形态和维持对刺激的复杂生理细胞反应。 特别是，我们的研究集中在受体酪氨酸激酶（RTK），这是许多多肽生长因子，细胞因子和激素的细胞表面受体，我们的身体用于正常生存。此外，我们还包括哺乳动物Toll样受体（TLR），这是一个识别病原体相关分子模式的受体家族。因此，必须严格控制这些受体对刺激的反应的强度和持续时间。各种报告表明，受体糖修饰实际上可能是连接受体结合、活化和细胞反应的无形联系。我的HQP学员已经确定了与激素诱导的受体激活过程相关的关键参与者。Neu1唾液酸酶被发现是一种必需的酶，其通过细胞表面上的共同受体水平信号传导途径来调节许多这些受体的活化。虽然Neu1和受体激活之间的精确关系尚未完全阐明，但它代表了该领域错过的细胞调控途径的新方法或开创性方法。如果成功，这些发现将对整个受体介导的细胞生物学领域具有重要意义。受体糖修饰对正常细胞活化至关重要，这一发现具有巨大的潜力，可用作HQP学员的研究工具，甚至可用于受体生物活性和下游细胞生理学的治疗调节。