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- W3100812302 abstract "Abstract Sonic Hedgehog (Shh) signaling is characterized by strict non-cell autonomy; cells expressing Shh do not respond to their ligand. Here, we identify several Shh mutations that gain the ability to activate the Hedgehog (Hh) pathway in cis . This activation requires the extracellular cysteine rich domain of Smoothened, but is otherwise independent of Ptch1/2. Many of the identified mutations disrupt either a highly conserved catalytic motif found in peptidases or an a-helix domain frequently mutated in holoprosencephaly-causing SHH alleles. The expression of gain-of-function mutants often results in the accumulation of unprocessed Shh pro-peptide, a form of Shh we demonstrate is sufficient to activate the Hh response cell-autonomously. Our results demonstrate that Shh is capable of activating the Hh pathway via Smo independently of Ptch1/2, and that it harbors an intrinsic mechanism that prevents cell-autonomous activation of the pathway to favor non-cell autonomous signaling." @default.
- W3100812302 created "2020-11-23" @default.
- W3100812302 creator A5033672356 @default.
- W3100812302 creator A5037110613 @default.
- W3100812302 date "2017-08-04" @default.
- W3100812302 modified "2023-09-26" @default.
- W3100812302 title "Gain-of-function Shh mutants activate Smo in cis independent of Ptch1/2 function" @default.
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- W3100812302 doi "https://doi.org/10.1101/172429" @default.
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