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Abstract
It has been recognized a long time ago that the hedgehog (Hh) and Wnt signaling pathways have numerous similarities that suggest their common evolutionary origin. Although the Hh and Wnt proteins are unrelated they are similar in as much as they carry lipid modifications that are critical for their interaction with their receptors. In our earlier work we have shown that Wnt inhibitory factor 1 (WIF1), originally identified as a Wnt antagonist also binds to and inhibits the signaling activity of sonic hedgehog (Shh), raising the possibility that the lipid moieties of these unrelated morphogens play a dominant role in their interaction with WIF1. In the present work we have compared the interactions of human WIF1 protein with lipidated and non-lipidated forms of human sonic hedgehog (Shh) using Surface Plasmon Resonance spectroscopy and reporter assays monitoring the signaling activity of human Shh. Our studies have shown that human WIF1 protein has significantly higher affinity for lipidated than non-lipidated Shh, indicating that lipid modifications of Hhs are important for interactions with WIF1.
Competing Interest Statement
The authors have declared no competing interest.
Abbreviations
- β-TrCP
- Beta-transducin repeat-containing protein
- C3H/10T1/2
- Cell line isolated from C3H mouse embryo, exhibiting fibroblast morphology, functionally similar to mesenchymal stem cells
- CHAPS
- 3-[(3-cholamidopropyl)dimethyl-ammonio]-1-propane sulfonate
- CK1
- Casein kinase 1
- DMEM
- Dulbecco minimal essential medium
- EC50
- Half maximal effective concentration
- EDTA
- Ethylenediaminetetraacetic acid
- GSK3β
- Glycogen synthase kinase 3β
- HEK
- Human Embryonic Kidney
- Hh
- Hedgehog
- NIH/3T3
- Fibroblast cell line isolated from NIH/Swiss mouse embryo
- PTCH1
- Patched-1 protein
- rhShh_1314-SH
- Non-lipidated recombinant human sonic hedgehog protein expressed in E. coli rhShh_1845-SH Non-lipidated recombinant human sonic hedgehog protein expressed in E. coli; Cys24 residue has been replaced by a hydrophobic Met-Ile-Ile sequence to mimic the hydrophobic palmitoyl moiety of dually lipidated sonic hedge-hog protein
- rhShh_8908-SH
- Recombinant dually lipidated human sonic hedgehog protein expressed in HEK cells
- rhWIF1
- Recombinant human WIF1
- Shh
- Sonic hedgehog
- WIF1
- Wnt inhibitory factor 1
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