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10.1038/nature14259 http://scihub22266oqcxt.onion/10.1038/nature14259 C4376489!4376489!25731175     free     free     free       Nature 2015 ; 519 (7542): 187-92 Nephropedia Template TP {{tp|p=25731175|t=2015. Notum deacylates Wnts to suppress signalling activity |pdf=|usr=}}{{25731175}} gab.com Text Notum deacylates Wnts to suppress signalling activity JO: Nature http://www.kidney.de/pget.php?&tw=1&pmid=25731175 #FOAvip Signalling by Wnts is finely balanced to ensure normal development and tissue homeostasis while avoiding diseases such as cancer. This is achieved in part by Notum, a highly conserved secreted feedback antagonist. Notum has been thought to act as a phospholipase, shedding glypicans and associated Wnts from the cell surface. However, this view fails to explain specificity since glypicans bind many extracellular ligands. Here we provide genetic evidence in Drosophila that Notum requires glypicans to suppress Wnt signalling, but does not cleave their glycophosphatidylinositol anchor. Structural analyses reveal glycosaminoglycan binding sites on Notum, which likely help Notum colocalise with Wnts. They also identify, at the active site of human and Drosophila Notum, a large hydrophobic pocket that accommodates palmitoleate. Kinetic and mass spectrometric analyses of human proteins show that Notum is a carboxylesterase that removes an essential palmitoleate moiety from Wnts and thus constitutes the first known extracellular protein deacylase. Twit Text FOAVip Notum deacylates Wnts to suppress signalling activity ????Nature http://www.kidney.de/pget.php?&tw=1&pmid=25731175 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=25731175 #FOAvip English Wikipedia <ref>{{Cite pmid|25731175}}</ref> Notum deacylates Wnts to suppress signalling activity #MMPMID25731175 Kakugawa S; Langton PF; Zebisch M; Howell S; Chang TH; Liu Y; Feizi T; Bineva G; O?Reilly N; Snijders AP; Jones EY; Vincent JP Nature 2015[Mar]; 519 (7542): 187-92 PMID25731175show ga Signalling by Wnts is finely balanced to ensure normal development and tissue homeostasis while avoiding diseases such as cancer. This is achieved in part by Notum, a highly conserved secreted feedback antagonist. Notum has been thought to act as a phospholipase, shedding glypicans and associated Wnts from the cell surface. However, this view fails to explain specificity since glypicans bind many extracellular ligands. Here we provide genetic evidence in Drosophila that Notum requires glypicans to suppress Wnt signalling, but does not cleave their glycophosphatidylinositol anchor. Structural analyses reveal glycosaminoglycan binding sites on Notum, which likely help Notum colocalise with Wnts. They also identify, at the active site of human and Drosophila Notum, a large hydrophobic pocket that accommodates palmitoleate. Kinetic and mass spectrometric analyses of human proteins show that Notum is a carboxylesterase that removes an essential palmitoleate moiety from Wnts and thus constitutes the first known extracellular protein deacylase. äNotum deacylates Wnts to suppress signalling activity (epmc).pdf DeepDyve Pubget Overpricing