Reference Report

Reference
Citation	Jia, J., Amanai, K., Wang, G., Tang, J., Wang, B., Jiang, J. (2002). Shaggy/GSK3 antagonizes Hedgehog signalling by regulating Cubitus interruptus. Nature 416(6880): 548--552. (Export to RIS)
FlyBase ID	FBrf0149689
Publication Type	Research paper
PubMed ID	11912487
PubMed Abstract	The Drosophila protein Shaggy (Sgg, also known as Zeste-white3, Zw3) and its vertebrate orthologue glycogen synthase kinase 3 (GSK3) are inhibitory components of the Wingless (Wg) and Wnt pathways. Here we show that Sgg is also a negative regulator in the Hedgehog (Hh) pathway. In Drosophila, Hh acts both by blocking the proteolytic processing of full-length Cubitus interruptus, Ci (Ci155), to generate a truncated repressor form (Ci75), and by stimulating the activity of accumulated Ci155 (refs 2-6). Loss of sgg gene function results in a cell-autonomous accumulation of high levels of Ci155 and the ectopic expression of Hh-responsive genes including decapentaplegic (dpp) and wg. Simultaneous removal of sgg and Suppressor of fused, Su(fu), results in wing duplications similar to those caused by ectopic Hh signalling. Ci is phosphorylated by GSK3 after a primed phosphorylation by protein kinase A (PKA), and mutating GSK3-phosphorylation sites in Ci blocks its processing and prevents the production of the repressor form. We propose that Sgg/GSK3 acts in conjunction with PKA to cause hyperphosphorylation of Ci, which targets it for proteolytic processing, and that Hh opposes Ci proteolysis by promoting its dephosphorylation.
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Language of Publication	English
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Publication Type	Journal
Abbreviation	Nature
Title	Nature
Publication Year	1869-
ISBN/ISSN	0028-0836
Data from Reference
Aberrations (2)
	Dp(1;2)w⁺70h Dp(1;3)w⁺67k
Alleles (24)
	arm^{Δ.Scer\UAS.T:Ivir\HA1} Avic\GFP^{hs.T:Hsap\MYC} ci^{-3P.Scer\UAS.W.T:Ivir\HA1} ci^{Cim1.Scer\UAS.T:Ivir\HA1} ci^{Cim2.Scer\UAS.T:Ivir\HA1} ci^{Cim3.Scer\UAS.T:Ivir\HA1} ci^{Scer\UAS.W.T:Ivir\HA1} cos^{Scer\UAS.T:Ivir\HA1} cos^{Scer\UAS.T:Zzzz\FLAG} Ecol\lacZ^ci-Dplac Ecol\lacZ^dpp.BS3.0 Ecol\lacZ^hh-P30 Ecol\lacZ^ptc.PG Ecol\lacZ^{wg.T:Zzzz\nls1} Mmus\Pkaca^mC.Scer\UAS Rnor\CD2^hs.PJ Scer\GAL4^Act5C.PP Scer\GAL4^Bx-MS1096 Scer\GAL4^{Scer\FRT.Rnor\CD2.Act5C} sgg³² smo³ Su(fu)^LP w^+mC Xlae\Gsk3β^DN.Scer\UAS
Constructs (17)
	P{BS3.0} P{GAL4-Act5C(FRT.CD2).P} P{GAL4-Act5C(-FRT).P} P{hsp70-CD2.J} P{hsp70-Myc-GFP} P{ptcA-lacZ} P{UAS-arm.Δ.flu} P{UAS-ci.Cim1} P{UAS-ci.Cim2} P{UAS-ci.Cim3} P{UAS-ci.HA.-3P} P{UAS-ci.HA.W} P{UAS-Cos2.FLAG} P{UAS-Cos2.W} P{UAS-PKA.mC} P{UAS-Xlae\Gsk3β.DN} P{wg-lacZ.nls}
Genes (18)
	arm Avic\GFP ci cos Ecol\lacZ Mmus\Pkaca Rnor\CD2 sc Scer\GAL4 sgg smo Su(fu) T:Hsap\MYC T:Ivir\HA1 T:Zzzz\FLAG T:Zzzz\nls1 w Xlae\Gsk3β
Insertions (3)
	P{GawB}Bx^MS1096 P{lacW}ci^Dplac P{PZ}hh^P30