The role of kinases in the Hedgehog signalling pathway

被引:47
作者
Aikin, Reid A. [1 ]
Ayers, Katie L. [1 ]
Therond, Pascal P. [1 ]
机构
[1] Univ Nice, Ctr Biochim, Inst Signalling Dev Biol & Canc Res, CNRS,UMR 6543, F-06108 Nice 02, France
关键词
Costal2; Fused; Hedgehog; kinase; phosphorylation;
D O I
10.1038/embor.2008.38
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The Hedgehog (Hh) signalling pathway has a crucial role in several developmental processes and is aberrantly activated in a variety of cancers. In Drosophila, many of the canonical Hh pathway components are phosphorylated, yet the precise role of these phosphorylation events in the regulation of Hh signal transduction is unclear. Furthermore, the Hh pathway receives input from several kinases that have well-described roles in other cellular functions, some of which have both positive and negative effects on Hh signalling. Several recent studies have characterized the role of specific phosphorylation events in the Hh pathway, and have begun to shed light on how phosphorylation of Hh signalling components affects their subcellular location, stability and activity to mediate the transcriptional response to the Hh gradient.
引用
收藏
页码:330 / 336
页数:7
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[11]   The fused protein kinase regulates Hedgehog-stimulated transcriptional activation in Drosophila Schneider 2 cells [J].
Fukumoto, T ;
Watanabe-Fukunaga, R ;
Fujisawa, K ;
Nagata, S ;
Fukunaga, R .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (42) :38441-38448
[12]   Protein kinase A is a common negative regulator of Hedgehog signaling in the vertebrate embryo [J].
Hammerschmidt, M ;
Bitgood, MJ ;
McMahon, AP .
GENES & DEVELOPMENT, 1996, 10 (06) :647-658
[13]   Communicating with Hedgehogs [J].
Hooper, JE ;
Scott, MP .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2005, 6 (04) :306-317
[14]   Signaling from Smo to Ci/Gli:: conservation and divergence of Hedgehog pathways from Drosophila to vertebrates [J].
Huangfu, D ;
Anderson, KV .
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[15]   Smoothened transduces Hedgehog signal by physically interacting with Costal2/Fused complex through its C-terminal tail [J].
Jia, JH ;
Tong, C ;
Jiang, J .
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[16]   Shaggy/GSK3 antagonizes Hedgehog signalling by regulating Cubitus interruptus [J].
Jia, JH ;
Amanal, K ;
Wang, GL ;
Tang, J ;
Wang, B ;
Jiang, J .
NATURE, 2002, 416 (6880) :548-552
[17]   Hedgehog signalling activity of Smoothened requires phosphorylation by protein kinase A and casein kinase I [J].
Jia, JH ;
Tong, C ;
Wang, B ;
Luo, LP ;
Jiang, J .
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[18]   Regulation of the Hedgehog and Wingless signalling pathways by the F-box/WD40-repeat protein Slimb [J].
Jiang, J ;
Struhl, G .
NATURE, 1998, 391 (6666) :493-496
[19]   Genetic dissection of the drosophila Cubitus interruptus signaling complex [J].
Lefers, MA ;
Wang, QT ;
Holmgren, RA .
DEVELOPMENTAL BIOLOGY, 2001, 236 (02) :411-420
[20]   Fused-Costal2 protein complex regulates Hedgehog-induced Smo phosphorylation and cell-surface accumulation [J].
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Cao, Xuesong ;
Jiang, Jin ;
Jia, Jianhang .
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