ArticleGenes & development2007
Fused-Costal2 protein complex regulates Hedgehog-induced Smo phosphorylation and cell-surface accumulation.
Article in Genes & development, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
38 citing papers in PubMed, 68 citations in OpenAlex.
- Hedgehog pathway, cell cycle, and primary cilium.Cell death discovery · 2025Review
- Alterations of ceramide synthesis induce PD-L1 internalization and signaling to regulate tumor metastasis and immunotherapy response.Cell reports · 2024Article
- Ulk4 promotes Shh signaling by regulating Stk36 ciliary localization and Gli2 phosphorylation.eLife · 2023Article
- Genetic variants in the Hedgehog signaling pathway genes are associated with gastric cancer risk in a Chinese Han population.Journal of biomedical research · 2021Article
- Expression and purification of fused kinase from insect cells forSTAR protocols · 2021Article
- An intracellular activation of Smoothened that is independent of Hedgehog stimulation inJournal of cell science · 2018Article
- SUMO regulates the activity of Smoothened and Costal-2 in Drosophila Hedgehog signaling.Scientific reports · 2017Article
- Regulation of Smoothened Trafficking and Hedgehog Signaling by the SUMO Pathway.Developmental cell · 2016Article
- Article
- Ubr3, a Novel Modulator of Hh Signaling Affects the Degradation of Costal-2 and Kif7 through Poly-ubiquitination.PLoS genetics · 2016Article
- Smoothened regulation in response to Hedgehog stimulation.Frontiers in biology · 2015Article
- The role of hedgehog signalling in skeletal health and disease.Nature reviews. Rheumatology · 2015Review
- Contributions of Costal 2-Fused interactions to Hedgehog signaling in Drosophila.Development (Cambridge, England) · 2015Article
- A Comparison of Ci/Gli Activity as Regulated by Sufu in Drosophila and Mammalian Hedgehog Response.PloS one · 2015Article
- Hedgehog induces formation of PKA-Smoothened complexes to promote Smoothened phosphorylation and pathway activation.Science signaling · 2014Article
- Suppressor of fused impedes Ci/Gli nuclear import by opposing Trn/Kapβ2 in Hedgehog signaling.Journal of cell science · 2014Article
- Decoding the phosphorylation code in Hedgehog signal transduction.Cell research · 2013Review
- Positive and negative regulation of Gli activity by Kif7 in the zebrafish embryo.PLoS genetics · 2013Article
- The Hedgehog signal transduction network.Science signaling · 2012Review
- Ligand-independent activation of the Hedgehog pathway displays non-cell autonomous proliferation during eye development in Drosophila.Mechanisms of development · 2012Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
The seven-transmembrane protein Smoothened (Smo) acts as a signal transducer in the Hedgehog (Hh) pathway that mediates many key developmental processes. In Drosophila, Hh-induced phosphorylation promotes Smo cell-surface accumulation and signaling activity; however, the mechanisms controlling Smo phosphorylation and cell-surface accumulation are still unknown. The intracellular signaling complex containing Fused (Fu) and Costal2 (Cos2) is thought to transduce the Hh signal downstream from Smo. Here, we identify a novel feedback mechanism that regulates Smo through the Fu-Cos2 complex. We found that Hh-induced Smo accumulation is inhibited in fu mutant clones or by expressing a dominant-negative form of Fu, and such inhibition is alleviated by removal of Cos2. Conversely, overexpressing Cos2 blocks Smo accumulation, which is reversed by coexpressing Fu. Cos2 blocks Smo accumulation through its C-terminal Smo-interacting domain, and Fu antagonizes Cos2 by phosphorylating Cos2 at Ser572. Furthermore, we found that Ser572 phosphorylation attenuates the Cos2-Smo interaction and promotes Cos2 instability. Finally, we provided evidence that Fu and Cos2 control Smo cell-surface accumulation by regulating Smo phosphorylation. Our data suggest that Cos2-Smo interaction blocks Hh-induced Smo phosphorylation, and that Fu promotes Smo phosphorylation by antagonizing Cos2.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.