Miura Grant I, Treisman Jessica E
Skirball Institute for Biomolecular Medicine and Department of Cell Biology, New York University School of Medicine, New York 10016, USA.
Cell Cycle. 2006 Jun;5(11):1184-8. doi: 10.4161/cc.5.11.2804. Epub 2006 Jun 1.
Proteins of the Hedgehog, Wnt and Epidermal Growth Factor Receptor (EGFR) ligand families are secreted signals that induce concentration-dependent responses in surrounding cells. Although these proteins must diffuse through the aqueous extracellular environment, recent work has shown that hydrophobic lipid modifications are essential for their functions. All three classes of ligands are palmitoylated in the secretory pathway by related enzymes, and Hedgehog also carries a C-terminal cholesterol modification as a result of its autocatalytic cleavage. Palmitoylation is required for Wingless secretion and contributes to the signaling activity of Hedgehog and Wnt3a, but is not required for secretion or receptor activation by the EGFR ligand Spitz. While lipid modifications enhance the long-range activity of Sonic hedgehog, they restrict the range and increase the local concentration of Spitz. We discuss the diverse functions and the possible extent of palmitoylation of secreted ligands.
刺猬索尼克（Hedgehog）、Wnt和表皮生长因子受体（EGFR）配体家族的蛋白质是分泌性信号，可诱导周围细胞产生浓度依赖性反应。尽管这些蛋白质必须在水性细胞外环境中扩散，但最近的研究表明，疏水性脂质修饰对其功能至关重要。所有这三类配体在分泌途径中都由相关酶进行棕榈酰化修饰，并且由于刺猬索尼克的自催化切割，它还带有一个C端胆固醇修饰。棕榈酰化修饰对于无翅型（Wingless）的分泌是必需的，并且有助于刺猬索尼克和Wnt3a的信号传导活性，但对于EGFR配体斯皮茨（Spitz）的分泌或受体激活并非必需。虽然脂质修饰增强了音猬因子（Sonic hedgehog）的远距离活性，但它们限制了斯皮茨的作用范围并增加了其局部浓度。我们讨论了分泌性配体棕榈酰化修饰的多种功能以及可能的程度。
