Hedgehog(Hh)信号通路对胚胎发育和成体组织器官的功能维持都十分重要，其功能的缺失常常导致各种肿瘤的发生，包括基底细胞瘤、髓母细胞瘤、结肠癌和肺癌等。Hh的受体蛋白是12跨膜蛋白Patched(Ptc)，当与Hh结合以后，其对Hh信号通路信号传递分子，7次跨膜的G蛋白偶联受体蛋白Smoothened(Smo)的抑制功能得以释放，从而导致Smo被高度磷酸化并发生空间构象的改变。修饰后的Smo被激活从而有效地传递上游信号给下游转录因子Cubitus interruptus(Ci)/Gli，活化后的全长的转录因子Ci/Gli可以进一步激活Hh信号通路下游基因的表达。磷酸化在Hh信号通路中起着十分重要的作用，Hh蛋白作为一种成形素（morphogen）,其不同浓度可以调控Hh信号通路核心分子（比如Smo, Cos2/Fu等）的不同磷酸化水平，从而有效控制下游基因的不同表达水平。中国科学院昆明动物研究所肿瘤信号转导研究组陈勇彬研究员，长期从事Hh信号通路的研究并在该领域获得了较好的研究成果，受Cell Research邀请撰写了Hh信号通路的综述，总结了近几年磷酸化在Hh信号通路中的功能研究，并比较了哺乳动物与果蝇系统中Hh信号通路相似与不同之处。（生物谷Bioon.com）
doi: 10.1038/cr.2013.10
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Decoding the phosphorylation code in Hedgehog signal transduction
Chen Y, Jiang J.
Hedgehog (Hh) signaling plays pivotal roles in embryonic development and adult tissue homeostasis, and its deregulation leads to numerous human disorders including cancer. Binding of Hh to Patched (Ptc), a twelve-transmembrane protein, alleviates its inhibition of Smoothened (Smo), a seven-transmembrane protein related to G-protein-coupled receptors (GPCRs), leading to Smo phosphorylation and activation. Smo acts through intracellular signaling complexes to convert the latent transcription factor Cubitus interruptus (Ci)/Gli from a truncated repressor to a full-length activator, leading to derepression/activation of Hh target genes. Increasing evidence suggests that phosphorylation participates in almost every step in the signal relay from Smo to Ci/Gli, and that differential phosphorylation of several key pathway components may be crucial for translating the Hh morphogen gradient into graded pathway activities. In this review, we focus on the multifaceted roles that phosphorylation plays in Hh signal transduction, and discuss the conservation and difference between Drosophila and mammalian Hh signaling mechanisms.
