G protein–coupled receptors control the sensitivity of cells to the morphogen Sonic Hedgehog
Open accessAbstract
Gα s protein–coupled receptors reduce the sensitivity of cells to the morphogen Sonic Hedgehog.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Premature SHH signalling resulting from disruption of GPR161 causes defects in limb and skeletal morphogenesis, cerebellar granule cell hyperproliferation and formation of SHH-subtype medulloblastoma.
“The importance of HH pathway repression is illustrated by the finding that premature SHH signalling resulting from disruption of GPR161 causes defects in limb and skeletal morphogenesis 134, cerebellar granule cell hyper-proliferation and formation of SHH-subtype medulloblastoma 135.”
From Cellular signalling by primary cilia in development, organ function and disease (2019) · cites this paper as [135]
The Results section on GPR161 in neural progenitor cells (page unavailable) reports that GPR161 loss increases Hedgehog signalling and alters neural progenitor specification. The Introduction mentions limb-bud patterning by Hedgehog ligands, but our copy does not link GPR161 disruption to limb or skeletal defects. The cerebellar proliferation and medulloblastoma findings carry a separate citation (135), so they are not attributed to this source. (LLM, conf=0.82)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Genome engineering using the CRISPR-Cas9 system
Ran, F. A., Hsu, P. D., Wright, J., Agarwala, V., Scott, D. A., & Zhang, F. (2013) · Nature Protocols · doi:10.1038/nprot.2013.143 · Cited by 11,133 · see citing works
Neuronal specification in the spinal cord: inductive signals and transcriptional codes
Jessell, T. M. (2000) · Nature Reviews Genetics · doi:10.1038/35049541 · Cited by 2,089 · see citing works
Lentivirus-delivered stable gene silencing by RNAi in primary cells.
Stewart, S. A., Dykxhoorn, D. M., Palliser, D., Mizuno, H., Yu, E. Y., An, D., Sabatini, D., Chen, I. S. Y., Hahn, W., Sharp, P., et al. (2003) · RNA: A publication of the RNA Society · doi:10.1261/rna.2192803 · Cited by 1,619 · see citing works
Vertebrate Smoothened functions at the primary cilium
Corbit, K. C., Aanstad, P., Singla, V., Norman, A. R., Stainier, D. Y. R., & Reiter, J. F. (2005) · Nature · doi:10.1038/nature04117 · Cited by 1,481 · see citing works
Patched1 Regulates Hedgehog Signaling at the Primary Cilium
Rohatgi, R., Milenkovic, L., & Scott, M. P. (2007) · Science · doi:10.1126/science.1139740 · Cited by 1,426 · see citing works
Self-citationG PROTEIN–COUPLED RECEPTOR KINASES
Pitcher, J. A., Freedman, N. J., & Lefkowitz, R. J. (1998) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.67.1.653 · Cited by 1,379 · see citing works
Wang, B., Fallon, J. F., & Beachy, P. A. (2000) · Cell · doi:10.1016/s0092-8674(00)80678-9 · Cited by 1,014 · see citing works
Smoothened Mutation Confers Resistance to a Hedgehog Pathway Inhibitor in Medulloblastoma
Yauch, R. L., Dijkgraaf, G. J. P., Alicke, B., Januario, T., Ahn, C. P., Holcomb, T., Pujara, K., Stinson, J., Callahan, C. A., Tang, T. T.-L., et al. (2009) · Science · doi:10.1126/science.1179386 · Cited by 841 · see citing works
Gli Proteins in Development and Disease
Hui, C., & Angers, S. (2011) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-092910-154048 · Cited by 693 · see citing works
Interpretation of the sonic hedgehog morphogen gradient by a temporal adaptation mechanism
Dessaud, É., Yang, L. L., Hill, K., Cox, B., Ulloa, F., Ribeiro, A., Mynett, A., Novitch, B. G., & Briscoe, J. (2007) · Nature · doi:10.1038/nature06347 · Cited by 613 · see citing works
Self-citationMukhopadhyay, S., Wen, X., Ratti, N., Loktev, A., Rangell, L., Scales, S. J., & Jackson, P. K. (2013) · Cell · doi:10.1016/j.cell.2012.12.026 · Cited by 486 · see citing works
Svärd, J., Henricson, K. H., Persson-Lek, M., Rozell, B., Lauth, M., Bergström, Å., Ericson, J., Toftgård, R., & Teglund, S. (2006) · Developmental Cell · doi:10.1016/j.devcel.2005.12.013 · Cited by 468 · see citing works
Humke, E. W., Dorn, K. V., Milenkovic, L., Scott, M. P., & Rohatgi, R. (2010) · Genes & Development · doi:10.1101/gad.1902910 · Cited by 444 · see citing works
Self-citationG protein-coupled receptor kinases: More than just kinases and not only for GPCRs
Gurevich, E. V., Tesmer, J. J. G., Mushegian, A. R., & Gurevich, V. V. (2011) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2011.08.001 · Cited by 422 · see citing works
Smoothened Variants Explain the Majority of Drug Resistance in Basal Cell Carcinoma
Atwood, S. X., Sarin, K. Y., Whitson, R. J., Li, J., Kim, G., Rezaee, M., Ally, M. S., Kim, J., Yao, C., Chang, A. L. S., et al. (2015) · Cancer Cell · doi:10.1016/j.ccell.2015.02.002 · Cited by 400 · see citing works
Tukachinsky, H., Lopez, L. V., & Salic, A. N. (2010) · The Journal of Cell Biology · doi:10.1083/jcb.201004108 · Cited by 388 · see citing works
Genomic Analysis of Smoothened Inhibitor Resistance in Basal Cell Carcinoma
Sharpe, H. J., Pau, G., Dijkgraaf, G. J. P., Basset‐Séguin, N., Modrusan, Z. D., Januario, T., Tsui, V., Durham, A. B., Dlugosz, A. A., Haverty, P. M., et al. (2015) · Cancer Cell · doi:10.1016/j.ccell.2015.02.001 · Cited by 384 · see citing works
Dijkgraaf, G. J. P., Alicke, B., Weinmann, L., Januario, T., West, K. A., Modrusan, Z. D., Burdick, D., Goldsmith, R. A., Robarge, K. D., Sutherlin, D., et al. (2010) · Cancer Research · doi:10.1158/0008-5472.can-10-2876 · Cited by 365 · see citing works
Gouti, M., Tsakiridis, A., Wymeersch, F. J., Huang, Y., Kleinjung, J., Wilson, V. A., & Briscoe, J. (2014) · PLoS Biology · doi:10.1371/journal.pbio.1001937 · Cited by 364 · see citing works
Self-citationStructural basis of Smoothened regulation by its extracellular domains
Byrne, E. F. X., Sircar, R., Miller, P. S., Hedger, G., Luchetti, G., Nachtergaele, S., Tully, M. D., Mydock-McGrane, L. K., Covey, D. F., Rambo, R. P., et al. (2016) · Nature · doi:10.1038/nature18934 · Cited by 361 · see citing works
Self-citationNovitch, B. G., Wichterle, H., Jessell, T. M., & Sockanathan, S. (2003) · Neuron · doi:10.1016/j.neuron.2003.08.006 · Cited by 350 · see citing works
Kim, J., Aftab, B. T., Tang, J. Y., Kim, D., Lee, A. H., Rezaee, M., Kim, J., Chen, B., King, E. M., Borodovsky, A., et al. (2013) · Cancer Cell · doi:10.1016/j.ccr.2012.11.017 · Cited by 346 · see citing works
Dorsal-ventral patterning of the spinal cord requires Gli3 transcriptional repressor activityPreprint
Persson, M., Stamataki, D., Welscher, P. T., Andersson, E., Böse, J., Rüther, U., Ericson, J., & Briscoe, J. (2002) · Genes & Development · doi:10.1101/gad.243402 · Cited by 306 · see citing works
Self-citationSingle-copy transgenic mice with chosen-site integration.
Bronson, S. K., Plaehn, E. G., Kluckman, K. D., et al. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.17.9067 · Cited by 296 · see citing works
Activity-Dependent Internalization of Smoothened Mediated by ß-Arrestin 2 and GRK2
Chen, W., Ren, X.-R., Nelson, C. D., Barak, L. S., Chen, J., Beachy, P. A., de Sauvage, F. J., & Lefkowitz, R. J. (2004) · Science · doi:10.1126/science.1104135 · Cited by 279 · see citing works
Cholesterol activates the G-protein coupled receptor Smoothened to promote Hedgehog signaling
Luchetti, G., Sircar, R., Kong, J. H., Nachtergaele, S., Sagner, A., Byrne, E. F. X., Covey, D. F., Siebold, C., & Rohatgi, R. (2016) · eLife · doi:10.7554/elife.20304 · Cited by 256 · see citing works
Self-citationActivation of heterotrimeric G proteins by Smoothened
Galdo, N. A. R., Saucy, B., DiLizio, C., & Manning, D. R. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0600880103 · Cited by 244 · see citing works
Gli Protein Activity Is Controlled by Multisite Phosphorylation in Vertebrate Hedgehog Signaling
Niewiadomski, P., Kong, J. H., Ahrends, R., Ma, Y., Humke, E. W., Khan, S., Teruel, M. N., Novitch, B. G., & Rohatgi, R. (2014) · Cell Reports · doi:10.1016/j.celrep.2013.12.003 · Cited by 239 · see citing works
Self-citationRibes, V., & Briscoe, J. (2009) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a002014 · Cited by 232 · see citing works
Self-citationChen, Y., Sasai, N., Ma, G., Yue, T., Jia, J., Briscoe, J., & Jiang, J. (2011) · PLoS Biology · doi:10.1371/journal.pbio.1001083 · Cited by 225 · see citing works
Self-citationActivation of Hedgehog signaling by loss of GNAS causes heterotopic ossification
Regard, J. B., Malhotra, D., Gvozdenovic‐Jeremic, J., Josey, M., Chen, M., Weinstein, L. S., Lü, J., Shore, E. M., Kaplan, F. S., & Yang, Y. (2013) · Nature Medicine · doi:10.1038/nm.3314 · Cited by 224 · see citing works
G protein Gαi functions immediately downstream of Smoothened in Hedgehog signalling
Ogden, S. K., Fei, D. L., Schilling, N. S., Ahmed, Y. F., Hwa, J., & Robbins, D. J. (2008) · Nature · doi:10.1038/nature07459 · Cited by 201 · see citing works
Tuson, M., He, M., & Anderson, K. V. (2011) · Development · doi:10.1242/dev.070805 · Cited by 192 · see citing works
GRK2: multiple roles beyond G protein-coupled receptor desensitization
Evron, T., Daigle, T. L., & Caron, M. G. (2012) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2011.12.003 · Cited by 154 · see citing works
Iglesias‐Bartolomé, R., Torres, D., Marone, R., Feng, X., Martı́n, D., Simaan, M., Chen, M., Weinstein, L. S., Taylor, S. S., Molinolo, A., et al. (2015) · Nature Cell Biology · doi:10.1038/ncb3164 · Cited by 147 · see citing works
Pal, K., Hwang, S.-H., Somatilaka, B., Badgandi, H., Jackson, P. K., DeFea, K., & Mukhopadhyay, S. (2016) · Journal of Cell Biology · doi:10.1083/jcb.201506132 · Cited by 141 · see citing works
Oosterveen, T., Kurdija, S., Alekseenko, Z., Uhde, C. W., Bergsland, M., Sandberg, M., Andersson, E., Dias, J. M. M., Muhr, J., & Ericson, J. (2012) · Developmental Cell · doi:10.1016/j.devcel.2012.09.015 · Cited by 132 · see citing works
G Protein-coupled Receptor Kinase 2/Gαq/11 Interaction
Sterne‐Marr, R., Tesmer, J. J. G., Day, P. W., et al. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m208787200 · Cited by 130 · see citing works
Molecular Mechanism of Selectivity among G Protein-Coupled Receptor Kinase 2 Inhibitors
Thal, D. M., Yeow, R. Y., Schoenau, C., Huber, J., & Tesmer, J. J. G. (2011) · Molecular Pharmacology · doi:10.1124/mol.111.071522 · Cited by 127 · see citing works
Smoothened Signal Transduction Is Promoted by G Protein-Coupled Receptor Kinase 2
Meloni, A. R., Fralish, G. B., Kelly, P., Salahpour, A., Chen, J., Wechsler‐Reya, R. J., Lefkowitz, R. J., & Caron, M. G. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.00546-06 · Cited by 121 · see citing works
The G protein α subunit Gαs is a tumor suppressor in Sonic hedgehog−driven medulloblastoma
He, X., Zhang, L., Chen, Y., Remke, M., Shih, D. J. H., Lu, F., Wang, H., Deng, Y., Yu, Y., Xia, Y., et al. (2014) · Nature Medicine · doi:10.1038/nm.3666 · Cited by 121 · see citing works
Cilia have high cAMP levels that are inhibited by Sonic Hedgehog-regulated calcium dynamics
Moore, B. S., Stepanchick, A. N., Tewson, P. H., Hartle, C. M., Zhang, J., Quinn, A. M., Hughes, T. E., & Mirshahi, T. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1602393113 · Cited by 120 · see citing works
Yu, J.-Z., & Rasenick, M. M. (2002) · Molecular Pharmacology · doi:10.1124/mol.61.2.352 · Cited by 113 · see citing works
Smoothened Activates Gαi-mediated Signaling in Frog Melanophores
DeCamp, D. L., Thompson, T., de Sauvage, F. J., & Lerner, M. R. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m004055200 · Cited by 101 · see citing works
Chen, Y., Li, S., Tong, C., Zhao, Y., Wang, B., Liu, Y., Jia, J., & Jiang, J. (2010) · Genes & Development · doi:10.1101/gad.1948710 · Cited by 99 · see citing works
Morphogen interpretation: the transcriptional logic of neural tube patterning
Cohen, M., Briscoe, J., & Blassberg, R. A. (2013) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2013.04.003 · Cited by 97 · see citing works
Self-citationLowe, J., Sanderson, H. S., Cooke, A. E., Ostovar, M., Tsisanova, E., Withey, S. L., Chavkin, C., Husbands, S. M., Kelly, E., Henderson, G., et al. (2015) · Molecular Pharmacology · doi:10.1124/mol.115.098293 · Cited by 90 · see citing works
Pusapati, G. V., Hughes, C. E., Dorn, K. V., Zhang, D., Sugianto, P., Aravind, L., & Rohatgi, R. (2014) · Developmental Cell · doi:10.1016/j.devcel.2014.01.021 · Cited by 88 · see citing works
Self-citationSmoothened Is a Fully Competent Activator of the Heterotrimeric G Protein Gi
Shen, F., Cheng, L., Douglas, A. E., Galdo, N. A. R., & Manning, D. R. (2013) · Molecular Pharmacology · doi:10.1124/mol.112.082511 · Cited by 71 · see citing works
Smoothened Signaling in Vertebrates Is Facilitated by a G Protein-coupled Receptor Kinase
Philipp, M., Fralish, G. B., Meloni, A. R., Chen, W., MacInnes, A. W., Barak, L. S., & Caron, M. G. (2008) · Molecular Biology of the Cell · doi:10.1091/mbc.e08-05-0448 · Cited by 66 · see citing works
Structural insights into G protein-coupled receptor kinase function
Homan, K. T., & Tesmer, J. J. G. (2013) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2013.10.009 · Cited by 65 · see citing works
Role of the Amino Terminus of G Protein-Coupled Receptor Kinase 2 in Receptor Phosphorylation
Pao, C. S., Barker, B. L., & Benovic, J. (2009) · Biochemistry · doi:10.1021/bi900408g · Cited by 61 · see citing works
Sonic Hedgehog-induced Proliferation Requires Specific Gα Inhibitory Proteins
Barzi, M., Kostrz, D. N., Menéndez, A., & Pons, S. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.178772 · Cited by 51 · see citing works
An essential role for Grk2 in Hedgehog signalling downstream of Smoothened
Zhao, Z., Lee, R. T. H., Pusapati, G. V., Iyu, A., Rohatgi, R., & Ingham, P. W. (2016) · EMBO Reports · doi:10.15252/embr.201541532 · Cited by 51 · see citing works
Self-citationCiliary Adenylyl Cyclases control the Hedgehog pathway
Vuolo, L., Herrera, A., Torroba, B., Menéndez, A., & Pons, S. (2015) · Journal of Cell Science · doi:10.1242/jcs.172635 · Cited by 50 · see citing works
Mapping the Putative G Protein-coupled Receptor (GPCR) Docking Site on GPCR Kinase 2
Beautrait, A., Michalski, K. R., Lopez, T., Mannix, K. M., McDonald, D., Cutter, A. R., Medina, C. B., Hebert, A., Francis, C. J., Bouvier, M., et al. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.593178 · Cited by 36 · see citing works
A Predictive Model of Bifunctional Transcription Factor Signaling during Embryonic Tissue Patterning
Junker, J. P., Peterson, K. A., Nishi, Y., Mao, J., McMahon, A. P., & van Oudenaarden, A. (2014) · Developmental Cell · doi:10.1016/j.devcel.2014.10.017 · Cited by 32 · see citing works
Neuropilin-2 contributes to tumorigenicity in a mouse model of Hedgehog pathway medulloblastoma
Gephart, M. H., Su, Y. S., Bandara, S., et al. (2013) · Journal of Neuro-Oncology · doi:10.1007/s11060-013-1216-1 · Cited by 26 · see citing works
Hwang, S., & Mukhopadhyay, S. (2015) · Birth Defects Research Part A: Clinical and Molecular Teratology · doi:10.1002/bdra.23267 · Cited by 20 · see citing works
Flagged first, then by citations
Research works printed but not linked: 2
- [37]Philipp M Fralish GB Meloni AR Chen W MacInnes AW Barak LS Caron MG Smoothened signaling in vertebrates is facilitated by a G protein-coupled receptor kinase Mol Biol Cell 2008 19 5478 5489 18815277 PMC2592680
- [38]Wang B Fallon JF Beachy PA Hedgehog-Regulated Processing of Gli3 Produces an Anterior/Posterior Repressor Gradient in the Developing Vertebrate Limb Cell 2000 100 423 434 10693759
Cited by
Sorted by citations
Cellular signalling by primary cilia in development, organ function and disease
Anvarian, Z., Mykytyn, K., Mukhopadhyay, S., Pedersen, L. B., & Christensen, S. T. (2019) · Nature Reviews Nephrology · doi:10.1038/s41581-019-0116-9 · Cited by 845 · see citing works
- Authors
- Pusapati, G. V., Kong, J. H., Patel, B. B., Gouti, M., Sagner, A., Sircar, R., Luchetti, G., Ingham, P. W., Briscoe, J., & Rohatgi, R.
- Affiliations
- Stanford Medicine (US)
- The Francis Crick Institute (GB)
- Nanyang Technological University (SG)
- Corresponding author
- Pusapati, Ganesh V.
- Kong, Jennifer H.
- Rohatgi, Rajat
- ORCID
- Venue
- Science Signaling
- Published
- 2018-02-06
- Volume
- 11
- Issue
- 516
- ISSN
- 1937-9145 (ISSN-L)
- 1945-0877
- PMC
- PMC5828112
- OpenAlex
- W2785474701
- Cited by
- 91
- References
- 59
- Citations by year
- 2026: 6 · 2025: 10 · 2024: 12 · 2023: 6 · 2022: 9 · 2021: 14 · 2020: 14 · 2019: 14 · 2018: 6
- FWCI
- 4.27
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science Signaling (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Research Explorer (The University of Manchester) (submittedVersion, other-oa)
- Funders
- National Institutes of Health (award343370, GM105448, award343371, GM112988, award343372, GM118082)
- American Heart Association (award343378, 14POST20370057)
- Human Frontier Science Program (award343382, LT000401/2014-L)
- Wellcome Trust (award343376, FC001051; WT098326MA)
- Biotechnology and Biological Sciences Research Council (award343373, BB/J015539/1)
- Toh Kian Chui foundation (award343377, N/A)
- Cancer Research UK (award343374, FC001051)
- Medical Research Council UK (award343375, FC001051)
- Helmholtz Association (award343381, N/A)
- Stanford School of Medicine Dean’s postdoctoral fellowship (award343379, N/A)
- Stanford Jump Start Award for Excellence in Research (award343380, N/A)
- European Union’s Seventh Framework Programme (award343383, 624973)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Hedgehog Signaling Pathway Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Keywords
- G protein-coupled receptors, Sonic hedgehog, morphogen signaling, Gs protein, receptor sensitivity, Hedgehog signaling
- MeSH terms
- Smoothened Receptor, Animals, Cells, Cultured, Chromogranins, Epistasis, Genetic, Humans, Signal Transduction, Cyclic AMP-Dependent Protein Kinases, GTP-Binding Protein alpha Subunits, Gs, NIH 3T3 Cells, Receptors, G-Protein-Coupled, Mice, Hedgehog Proteins, G-Protein-Coupled Receptor Kinase 2, HEK293 Cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
