ArticleThe Journal of biological chemistry2011
Growth Arrest Specific 8 (Gas8) and G protein-coupled receptor kinase 2 (GRK2) cooperate in the control of Smoothened signaling.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 33 citations in OpenAlex.
- Single cell transcriptomics reveals dendritic cell subsets in bovine afferent lymph and immune cell-resolved responses to BCG vaccination.Frontiers in immunology · 2026Article
- Analysis of insertion/deletion variation of litter size in Guizhou black goat.Tropical animal health and production · 2025Article
- Hepatocyte Smoothened Activity Controls Susceptibility to Insulin Resistance and Nonalcoholic Fatty Liver Disease.Cellular and molecular gastroenterology and hepatology · 2023Article
- PCD Genes-From Patients to Model Organisms and Back to Humans.International journal of molecular sciences · 2022Review
- Trypanin Disruption Affects the Motility and Infectivity of the ProtozoanFrontiers in cellular and infection microbiology · 2021Article
- Variant profiles of genes mapping to chromosome 16q loss in Wilms tumors reveals link to cilia-related genes and pathways.Genes & cancer · 2020Article
- Mutations in GRK2 cause Jeune syndrome by impairing Hedgehog and canonical Wnt signaling.EMBO molecular medicine · 2020Article
- RPSAP52 lncRNA Inhibits p21Waf1/CIP Expression by Interacting With the RNA Binding Protein HuR.Oncology research · 2020Article
- The pseudogene URAHP promotes proliferation and regulates the pathogenesis of preeclampsia.American journal of translational research · 2020Article
- GRK2 promotes growth of medulloblastoma cells and protects them from chemotherapy-induced apoptosis.Scientific reports · 2019Article
- Pharmacological cholesterol depletion disturbs ciliogenesis and ciliary function in developing zebrafish.Communications biology · 2019Article
- Role of canonical Hedgehog signaling pathway in liver.International journal of biological sciences · 2018Review
- Evolutionary Proteomics Uncovers Ancient Associations of Cilia with Signaling Pathways.Developmental cell · 2017Article
- The hydrolethalus syndrome protein HYLS-1 regulates formation of the ciliary gate.Nature communications · 2016Article
- Mutation of Growth Arrest Specific 8 Reveals a Role in Motile Cilia Function and Human Disease.PLoS genetics · 2016Article
- Ins and outs of GPCR signaling in primary cilia.EMBO reports · 2015Review
- Phenotypic regulation of the sphingosine 1-phosphate receptor miles apart by G protein-coupled receptor kinase 2.Biochemistry · 2015Article
- Overlapping and opposing functions of G protein-coupled receptor kinase 2 (GRK2) and GRK5 during heart development.The Journal of biological chemistry · 2014Article
- GRK2: multiple roles beyond G protein-coupled receptor desensitization.Trends in pharmacological sciences · 2012Review
- Axonemal positioning and orientation in three-dimensional space for primary cilia: what is known, what is assumed, and what needs clarification.Developmental dynamics : an official publication of the American Association of Anatomists · 2011Review
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
The G protein-coupled receptor (GPCR)-like molecule Smoothened (Smo) undergoes dynamic intracellular trafficking modulated by the microtubule associated kinase GRK2 and recruitment of β-arrestin. Of this trafficking, especially the translocation of Smo into primary cilia and back to the cytoplasm is essential for the activation of Hedgehog (Hh) signaling in vertebrates. The complete mechanism of this bidirectional transport, however, is not completely understood. Here we demonstrate that Growth Arrest Specific 8 (Gas8), a microtubule associated subunit of the Dynein Regulatory Complex (DRC), interacts with Smo to modulate this process. Gas8 knockdown in ciliated cells reduces Smo signaling activity and ciliary localization whereas overexpression stimulates Smo activity in a GRK2-dependent manner. The C terminus of Gas8 is important for both Gas8 interaction with Smo and facilitating Smo signaling. In zebrafish, knocking down Gas8 results in attenuated Hh transcriptional responses and impaired early muscle development. These effects can be reversed by the co-injection of Gas8 mRNA or by constitutive activation of the downstream Gli transcription factors. Furthermore, Gas8 and GRK2 display a synergistic effect on zebrafish early muscle development and some effects of GRK2 knockdown can be rescued by Gas8 mRNA. Interestingly, Gas8 does not interfere with cilia assembly, as the primary cilia architecture is unchanged upon Gas8 knock down or heterologous expression. This is in contrast to cells stably expressing both GRK2 and Smo, in which cilia are significantly elongated. These results identify Gas8 as a positive regulator of Hh signaling that cooperates with GRK2 to control Smo signaling.
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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.