ArticleMolecular and cellular biology2012
c-Src links a RANK/αvβ3 integrin complex to the osteoclast cytoskeleton.
Article in Molecular and cellular biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 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
43 citing papers in PubMed, 69 citations in OpenAlex.
- Integrin Signaling Imbalance in Periodontitis: A Stage-Dependent Link Between Inflammation, Bone Resorption and Regenerative Failure.Biomolecules · 2026Review
- Bone matrix proteins: regulators of skeletal remodeling and repair.Journal of bone and mineral metabolism · 2026Review
- Cell signaling and transcriptional regulation of osteoclast lineage commitment, differentiation, bone resorption and diseases.Cell discovery · 2026Review
- Hypergravity reduces F-actin accumulation in osteoclasts, with attenuated bone resorption.PloS one · 2026Article
- Swiprosin-1 Negatively Regulates Osteoclast Differentiation and Bone Resorption via Akt/MAPK/NF-κB Pathway and αvβ3 Integrin-Dependent Signaling.International journal of molecular sciences · 2025Article
- Cancer metastasis to the bone: Mechanisms and animal models (Review).Oncology letters · 2025Review
- Mechanistic insights into bone destruction in multiple myeloma: Cellular and molecular perspectives.Journal of bone oncology · 2025Review
- Trachelogenin alleviates osteoarthritis by inhibiting osteoclastogenesis and enhancing chondrocyte survival.Chinese medicine · 2024Article
- Osteoclast Methods in Protein Phosphatase Research.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Src tyrosine kinase promotes cardiac remodeling induced by chronic sympathetic activation.Bioscience reports · 2023Article
- Leucine Repeat Rich Kinase 1 Controls Osteoclast Activity by Managing Lysosomal Trafficking and Secretion.Biology · 2023Article
- Anti-Osteoporotic Effects ofMolecules (Basel, Switzerland) · 2021Article
- L-Plastin Phosphorylation: Possible Regulation by a TNFR1 Signaling Cascade in Osteoclasts.Cells · 2021Article
- Estrogen Decreases Cytoskeletal Organization by Forming an ERα/SHP2/c-Src Complex in Osteoclasts to Protect against Ovariectomy-Induced Bone Loss in Mice.Antioxidants (Basel, Switzerland) · 2021Article
- Review
- Heterogeneity and Actin Cytoskeleton in Osteoclast and Macrophage Multinucleation.International journal of molecular sciences · 2020Review
- Integrin-associated molecules and signalling cross talking in osteoclast cytoskeleton regulation.Journal of cellular and molecular medicine · 2020Review
- RACK1 interaction with c-Src is essential for osteoclast function.Experimental & molecular medicine · 2019Article
- Overview of RAW264.7 for osteoclastogensis study: Phenotype and stimuli.Journal of cellular and molecular medicine · 2019Review
- PGC1β Organizes the Osteoclast Cytoskeleton by Mitochondrial Biogenesis and Activation.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2018Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
RANK ligand (RANKL), by mechanisms unknown, directly activates osteoclasts to resorb bone. Because c-Src is key to organizing the cell's cytoskeleton, we asked if the tyrosine kinase also mediates RANKL-stimulated osteoclast activity. RANKL induces c-Src to associate with RANK(369-373) in an αvβ3-dependent manner. Furthermore, RANK(369-373) is the only one of six putative TRAF binding motifs sufficient to generate actin rings and activate the same cytoskeleton-organizing proteins as the integrin. While c-Src organizes the cell's cytoskeleton in response to the cytokine, it does not participate in RANKL-stimulated osteoclast formation. Attesting to their collaboration, αvβ3 and activated RANK coprecipitate, but only in the presence of c-Src. c-Src binds activated RANK via its Src homology 2 (SH2) domain and αvβ3 via its SH3 domain, suggesting the kinase links the two receptors. Supporting this hypothesis, deletion or inactivating point mutation of either the c-Src SH2 or SH3 domain obviates the RANK/αvβ3 association. Thus, activated RANK prompts two distinct signaling pathways; one promotes osteoclast formation, and the other, in collaboration with c-Src-mediated linkage to αvβ3, organizes the cell's cytoskeleton.
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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.