Role of unusual O-glycans in intercellular signaling.
Role of unusual O-glycans in intercellular signaling.
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DOI：
10.1016/j.biocel.2008.10.001
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发表时间：
2009-05
影响因子：
4
通讯作者：
Haltiwanger, Robert S.
中科院分区：
文献类型：
--
作者：
Luther, Kelvin B.;Haltiwanger, Robert S.
在过去的二十年里，我们对多糖在发育和信号转导中的作用的了解有了极大的扩展。虽然大多数工作都集中在N-连接或粘蛋白-O-连接的糖基化的重要性上，但最近的工作强调了几种更不寻常的糖基化形式的重要性，这是本综述的重点。特别是，Notch的表皮生长因子(EGF)重复序列上的O-岩藻糖聚糖调节信号的能力将糖基化与磷酸化结合起来，作为一种调节蛋白质-蛋白质相互作用及其产生的下游信号的手段。最近发现，Notch功能也需要对Notch EGF重复序列进行O-葡萄糖修饰，这进一步扩大了能够调节Notch信号的糖基化事件的范围。Notch在发育和后来的细胞命运决定中的重要作用强调了这些修饰在人类生物学中的重要性。随着发现凝血酶反应蛋白1型重复序列也被O-岩藻糖修饰，人们才刚刚开始了解多糖在细胞间信号事件中的作用，并似乎准备扩展到新的领域。最后，一种名为C-甘露糖基化的罕见形式的糖基化可以修饰一些有信号能力的分子中的色氨酸，这可能是该领域的进一步复杂性。我们将回顾这些领域中的每一个，重点是产生的多糖结构，它们存在的后果，以及负责的酶。
In the last two decades, our knowledge of the role of glycans in development and signal transduction has expanded enormously. While most work has focused on the importance of N-linked or mucin-type O-linked glycosylation, recent work has highlighted the importance of several more unusual forms of glycosylation that are the focus of this review. In particular, the ability of O-fucose glycans on the Epidermal Growth Factor-like (EGF) repeats of Notch to modulate signaling places glycosylation alongside phosphorylation as a means to modulate protein-protein interactions and their resultant downstream signals. The recent discovery that O-glucose modification of Notch EGF repeats is also required for Notch function has further expanded the range of glycosylation events capable of modulating Notch signaling. The prominent role of Notch during development and in later cell-fate decisions underscores the importance of these modifications in human biology. The role of glycans in intercellular signaling events is only beginning to be understood and appears ready to expand into new areas with the discovery that Thrombospondin type 1 repeats are also modified with O-fucose glycans. Finally, a rare form of glycosylation called C-mannosylation modifies tryptophans in some signaling competent molecules and may be a further layer of complexity in the field. We will review each of these areas focusing on the glycan structures produced, the consequence of their presence, and the enzymes responsible.
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