ArticleCell death and differentiation2018
STAC2 negatively regulates osteoclast formation by targeting the RANK signaling complex.
Article in Cell death and differentiation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 34 citations in OpenAlex.
- Low frequency sinusoidal electromagnetic fields promote the osteogenic differentiation of rat bone marrow mesenchymal stem cells by modulating miR-34b-5p/STAC2.Communications biology · 2024Article
- The histone methyltransferase ASH1L protects against bone loss by inhibiting osteoclastogenesis.Cell death and differentiation · 2024Article
- Modulation of fracture healing by senescence-associated secretory phenotype (SASP): a narrative review of the current literature.European journal of medical research · 2024Review
- Brevilin A inhibits RANKL-induced osteoclast differentiation and bone resorption.In vitro cellular & developmental biology. Animal · 2023Article
- Molecular interactions of STAC proteins with skeletal muscle dihydropyridine receptor and excitation-contraction coupling.Protein science : a publication of the Protein Society · 2022Article
- Effects ofEvidence-based complementary and alternative medicine : eCAM · 2022Article
- CYT387, a JAK-Specific Inhibitor Impedes Osteoclast Activity and Oophorectomy-Induced OsteoporosisFrontiers in pharmacology · 2022Article
- TRPV6 is a potential regulator of bone resorption in bone loss induced by estrogen deficiency.iScience · 2021Article
- Article
- Oroxin B Attenuates Ovariectomy-Induced Bone Loss by Suppressing Osteoclast Formation and Activity.Drug design, development and therapy · 2021Article
- The calcium channel TRPV6 is a novel regulator of RANKL-induced osteoclastic differentiation and bone absorption activity through the IGF-PI3K-AKT pathway.Cell proliferation · 2021Article
- Article
- Plasma proteomic profiling of young and old mice reveals cadherin-13 prevents age-related bone loss.Aging · 2020Article
- 2-NPPA Mitigates Osteoclastogenesis via Reducing TRAF6-Mediated c-fos Expression.Frontiers in pharmacology · 2020Article
- Stac Proteins Suppress CaThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- Allosteric regulators selectively prevent CaeLife · 2018Article
- RANKL signaling in bone marrow mesenchymal stem cells negatively regulates osteoblastic bone formation.Bone research · 2018Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The receptor activator of nuclear factor-κB (RANK) protein activates various protein kinase signaling cascades, including those involving NF-κB, mitogen-activated protein kinase (MAPK), and Bruton tyrosine kinase (Btk)/tyrosine-protein kinase Tec. However, the mechanism underlying the negative regulation of RANK by downstream signaling molecules remains unclear. Here, we report that Src homology 3 domain and cysteine-rich domain-containing protein 2 (STAC2) is a novel RANK ligand-inducible protein that negatively regulates RANK-mediated osteoclast formation. STAC2 physically interacts with RANK and inhibits the formation of the RANK signaling complex, which contains Grb-2-associated binder 2 (Gab2) and phospholipase Cγ2 (PLCγ2), thus leading to the suppression of RANK-mediated NF-κB and MAPK activation. Furthermore, STAC2 overexpression limits Btk/Tec-mediated PLCγ2 phosphorylation via the interaction between STAC2 and Btk/Tec. Taken together, our results reveal a novel mechanism whereby RANK signaling is restricted by its physical interaction with STAC2.
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