ArticleScience signaling2015
The scaffold protein RACK1 mediates the RANKL-dependent activation of p38 MAPK in osteoclast precursors.
Article in Science signaling, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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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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Who cites it
31 citing papers in PubMed, 50 citations in OpenAlex.
- TTC26 scaffolds MINDY3-mediated RACK1 deubiquitination to drive osteoclastogenesis and pathological bone resorption.Journal of orthopaedic translation · 2026Article
- G protein-coupled receptor 35 stimulation reduces osteoclast activity in primary human bone cells.JBMR plus · 2025Article
- Clustered peptide regulating the multivalent interaction between RANK and TRAF6 inhibits osteoclastogenesis by fine-tuning signals.Communications biology · 2025Article
- Ribosomal proteins: the missing piece in the inflammation puzzle?Molecular and cellular biochemistry · 2025Review
- C-X-C motif chemokine ligand 13 suppresses osteoclast differentiation via interference with RANKL-RANK interaction.Frontiers in immunology · 2025Article
- RACK1 enhances STAT3 stability and promotes T follicular helper cell development and function during blood-stage Plasmodium infection in mice.PLoS pathogens · 2024Article
- Single-cell transcriptomics reveals cell atlas and identifies cycling tumor cells responsible for recurrence in ameloblastoma.International journal of oral science · 2024Article
- A mixture ofHeliyon · 2024Article
- Skin chronological aging drives age-related bone loss via secretion of cystatin-A.Nature aging · 2022Article
- Methyl 3,4-dihydroxybenzoate inhibits RANKL-induced osteoclastogenesis via Nrf2 signalingActa biochimica et biophysica Sinica · 2022Article
- Nanoporous titanium implant surface promotes osteogenesis by suppressing osteoclastogenesis via integrin β1/FAKpY397/MAPK pathway.Bioactive materials · 2022Article
- DDIT4 S-Nitrosylation Aids p38-MAPK Signaling Complex Assembly to Promote Hepatic Reactive Oxygen Species Production.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Article
- Diversity and versatility of p38 kinase signalling in health and disease.Nature reviews. Molecular cell biology · 2021Review
- Inhibition of Sirtuin 3 prevents titanium particle-induced bone resorption and osteoclastsogenesis via suppressing ERK and JNK signaling.International journal of biological sciences · 2021Article
- ELMO1 Regulates RANKL-Stimulated Differentiation and Bone Resorption of Osteoclasts.Frontiers in cell and developmental biology · 2021Article
- New perspectives on traumatic bone infections.Chinese journal of traumatology = Zhonghua chuang shang za zhi · 2020Review
- Proteomics of regenerated tissue in response to a titanium implant with a bioactive surface in a rat tibial defect model.Scientific reports · 2020Article
- The role of Rho GTPases' substrates Rac and Cdc42 in osteoclastogenesis and relevant natural medicinal products study.Bioscience reports · 2020Review
- Artesunate inhibits osteoclastogenesis through the miR-503/RANK axis.Bioscience reports · 2020Article
- Roles of Cyclic AMP Response Element Binding Activation in the ERK1/2 and p38 MAPK Signalling Pathway in Central Nervous System, Cardiovascular System, Osteoclast Differentiation and Mucin and Cytokine Production.International journal of molecular sciences · 2019Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
The E3 ubiquitin ligase TRAF6 [tumor necrosis factor (TNF) receptor (TNFR)-associated factor 6] and the associated kinase TAK1 [transforming growth factor-β (TGF-β)-activated kinase 1] are key components of the signaling pathways that activate nuclear factor κB (NF-κB) and mitogen-activated protein kinases (MAPKs) in response to various stimuli. The cytokine RANKL (receptor activator of NF-κB ligand) is essential for the differentiation of bone marrow cells into bone-resorbing osteoclasts through the activation of NF-κB and MAPK. We found that the scaffold protein RACK1 (receptor for activated C kinase 1) selectively mediated the RANKL-dependent activation of p38 MAPK through the TRAF6-TAK1 axis by interacting with the MAPK kinase MKK6 (MAPK kinase kinase 6), which is upstream of p38 MAPK. RACK1 was necessary for the differentiation of bone marrow cells into osteoclasts through the stimulation of p38 MAPK activation. Osteoclast precursors exposed to RANKL exhibited an interaction among RACK1, RANK, TRAF6, TAK1, and the kinase MKK6, thereby leading to the activation of the MKK6-p38 MAPK pathway. Experiments in which RACK1 or TAK1 was knocked down in osteoclast precursors indicated that RACK1 acted as a bridge, bringing MKK6 to the TRAF6-TAK1 complex. Furthermore, local administration of RACK1-specific small interfering RNA (siRNA) into mice calvariae reduced the RANKL-induced bone loss by reducing the numbers of osteoclasts. These findings suggest that RACK1 specifies the RANKL-stimulated activation of p38 MAPK by facilitating the association of MKK6 with TAK1 and may provide a molecular target for a new therapeutic strategy to treat bone diseases.
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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.