The role of glycosylation in receptor activation

我们研究计划的本质是研究由许多蛋白质和受体表达的糖残基在细胞激活中的作用。这些糖残基具有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、形成细胞形态以及维持细胞对刺激的复杂生理反应。特别是，我们的研究重点是受体酪氨酸激酶(RTK)，它是许多多肽生长因子、细胞因子和激素的细胞表面受体，我们的身体用来正常生存。此外，我们还包括哺乳动物Toll样受体(TLRs)，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反应的强度和持续时间，这一点至关重要。各种报道表明，受体糖修饰实际上可能是连接受体结合、激活和细胞反应的无形纽带。我的HQP学员已经确定了激素诱导的受体激活过程(ES)中的关键角色。NEU1唾液酸酶被发现是一种重要的酶，它通过一个共同的受体水平的信号通路作用于细胞表面，调节许多这些受体的激活。虽然Neu1和受体激活之间的确切关系尚未完全阐明，但它代表了一种新的或开创性的细胞调控途径，而该领域一直未有报道。如果成功，这一发现将对受体介导的整个细胞生物学领域具有非常重要的意义。受体糖修饰对正常的细胞激活至关重要，这一发现具有巨大的潜力，可以作为HQP实习生的研究工具，甚至用于受体生物活性和下游细胞生理的治疗调节。

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.