Decoding the phosphorylation code in Hedgehog signal transduction  

作　　者：Yongbin Chen Jin Jiang 

机构地区：[1]Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kun-ming Institute of Zoology, Chinese Academy of Sciences, 32 Jiaochang Donglu, Kunming, Yunnan 650223, China [2]Department of Developmental Biology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA

出　　处：《Cell Research》2013年第2期186-200,共15页细胞研究（英文版）

基　　金：We apologize to those whose work we could not cite due to space limitations. Y Chen is supported by grams from the National Natural Science Foundation of China （31271579）, National Key Basic Research Program of China （2013CB910900）, American Heart Association postdoctoral fellowship （10POST3640046）, Kunming Institute of Zoology startup foundation and Chinese Academy of Sciences. J Jiang is supported by grants from NIH （GM067045 and GM061269）, CPRIT （RPI00561） and Welch foundation 0-1603）, and is a Eugene McDermott Endowed Schol-ar of Biomedical Science at UTSW.

摘　　要：Hedgehog （Hh） signaling plays pivotal roles in embryonic development and adult tissue homeostasis, and its de-regulation leads to numerous human disorders including cancer. Binding of Hh to Patched （Ptc）, a twelve-transmem- brane 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 phosphory-lation 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.Hedgehog （Hh） signaling plays pivotal roles in embryonic development and adult tissue homeostasis, and its de-regulation leads to numerous human disorders including cancer. Binding of Hh to Patched （Ptc）, a twelve-transmem- brane 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 phosphory-lation 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.

关 键 词：HEDGEHOG SMO GLI signal transduction PHOSPHORYLATION development cancer 

分 类 号：Q257[生物学—细胞生物学] Q51