Palmitoylation of the EGFR ligand spitz by rasp increases spitz activity by restricting its diffusion
Palmitoylation of the EGFR ligand spitz by rasp increases spitz activity by restricting its diffusion
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DOI：
10.1016/j.devcel.2005.11.017
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发表时间：
2006-02-01
影响因子：
11.8
通讯作者：
Treisman, JE
中科院分区：
文献类型：
--
作者：
Miura, GI;Buglino, J;Treisman, JE
脂质修饰如棕榈酰化或肉豆蔻酰化将细胞内蛋白质靶向细胞膜。Hedgehog和Wnt家族的分泌配体也被棕榈酰化;这种修饰需要相关的跨膜酰基转移酶Rasp和Porcupine，可以增强它们的分泌、运输或活性。我们在这里表明，锉刀也是必不可少的斯皮茨，果蝇表皮生长因子受体（EGFR）的配体的发育功能。在培养的细胞中，Rasp促进棕榈酸添加到Spitz的N-末端半胱氨酸残基，并且该半胱氨酸是Spitz体内活性所需的。棕榈酰化减少Spitz分泌并增强其质膜结合，但不改变其体外激活EGFR的能力。在体内，过度表达的非棕榈酰化Spitz具有增加的作用范围，但活性降低。这些数据表明棕榈酰化在限制Spitz扩散中的作用，使其局部浓度达到生物功能所需的阈值。
Lipid modifications such as palmitoylation or myristoylation target intracellular proteins to cell membranes. Secreted ligands of the Hedgehog and Wnt families are also palmitoylated; this modification, which requires the related transmembrane acyltransferases Rasp and Porcupine, can enhance their secretion, transport, or activity. We show here that rasp is also essential for the developmental functions of Spitz, a ligand for the Drosophila epidermal growth factor receptor (EGFR). In cultured cells, Rasp promotes palmitate addition to the N-terminal cysteine residue of Spitz, and this cysteine is required for Spitz activity in vivo. Palmitoylation reduces Spitz secretion and enhances its plasma membrane association, but does not alter its ability to activate the EGFR in vitro. In vivo, overexpressed unpalmitoylated Spitz has an increased range of action but reduced activity. These data suggest a role for palmitoylation in restricting Spitz diffusion, allowing its local concentration to reach the threshold required for biological function.