Hedgehog(Hh)信號通路對胚胎發(fā)育和成體組織器官的功能維持都十分重要，其功能的缺失常常導(dǎo)致各種腫瘤的發(fā)生,，包括基底細(xì)胞瘤,、髓母細(xì)胞瘤、結(jié)腸癌和肺癌等,。Hh的受體蛋白是12跨膜蛋白Patched(Ptc),，當(dāng)與Hh結(jié)合以后，其對Hh信號通路信號傳遞分子,，7次跨膜的G蛋白偶聯(lián)受體蛋白Smoothened(Smo)的抑制功能得以釋放,，從而導(dǎo)致Smo被高度磷酸化并發(fā)生空間構(gòu)象的改變。修飾后的Smo被激活從而有效地傳遞上游信號給下游轉(zhuǎn)錄因子Cubitus interruptus(Ci)/Gli,，活化后的全長的轉(zhuǎn)錄因子Ci/Gli可以進(jìn)一步激活Hh信號通路下游基因的表達(dá),。磷酸化在Hh信號通路中起著十分重要的作用，Hh蛋白作為一種成形素（morphogen）,其不同濃度可以調(diào)控Hh信號通路核心分子（比如Smo, Cos2/Fu等）的不同磷酸化水平，從而有效控制下游基因的不同表達(dá)水平,。中國科學(xué)院昆明動物研究所腫瘤信號轉(zhuǎn)導(dǎo)研究組陳勇彬研究員,，長期從事Hh信號通路的研究并在該領(lǐng)域獲得了較好的研究成果，受Cell Research邀請撰寫了Hh信號通路的綜述,，總結(jié)了近幾年磷酸化在Hh信號通路中的功能研究,，并比較了哺乳動物與果蠅系統(tǒng)中Hh信號通路相似與不同之處。（生物谷Bioon.com）
doi: 10.1038/cr.2013.10
PMC:
PMID:
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.
