ArticleMolecular and cellular biology2012
Cot kinase promotes Ca2+ oscillation/calcineurin-independent osteoclastogenesis by stabilizing NFATc1 protein.
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 14 papers.
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Who cites it
14 citing papers in PubMed, 21 citations in OpenAlex.
- DYRK1A and Parkinson's disease, facts and hypotheses.Neurobiology of disease · 2026Review
- The role of NPY2R/NFATc1/DYRK1A regulatory axis in sebaceous glands for sebum synthesis.Cellular & molecular biology letters · 2023Article
- The checkpoint inhibitor PD-1H/VISTA controls osteoclast-mediated multiple myeloma bone disease.Nature communications · 2023Article
- A circRNA-miRNA-mRNA network plays a role in the protective effect of diosgenin on alveolar bone loss in ovariectomized rats.BMC complementary medicine and therapies · 2020Article
- Tumor progression locus 2 (TPL2) in tumor-promoting Inflammation, Tumorigenesis and Tumor Immunity.Theranostics · 2020Review
- The roles of Orai and Stim in bone health and disease.Cell calcium · 2019Review
- Tmem178 acts in a novel negative feedback loop targeting NFATc1 to regulate bone mass.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- RelB-induced expression of Cot, an MAP3K family member, rescues RANKL-induced osteoclastogenesis in alymphoplasia mice by promoting NF-κB2 processing by IKKα.The Journal of biological chemistry · 2014Article
- Novel role for NFAT3 in ERK-mediated regulation of CXCR4.PloS one · 2014Article
- Vitamin D endocrine system and osteoclasts.BoneKEy reports · 2014Article
- Treatment with Rhizoma Dioscoreae extract has protective effect on osteopenia in ovariectomized rats.TheScientificWorldJournal · 2014Article
- Article
- Regulation of osteoclasts by membrane-derived lipid mediators.Cellular and molecular life sciences : CMLS · 2013Review
- Molecular mechanisms of triggering, amplifying and targeting RANK signaling in osteoclasts.World journal of orthopedics · 2012Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Osteoclasts are multinuclear bone-resorbing cells formed by the fusion of monocyte/macrophage-lineage precursor cells. Activation of the transcription factor NFATc1 (nuclear factor of activated T cells c1) by the receptor activator of NF-κB ligand (RANKL) is critical for osteoclast differentiation. In our previous report (Y. Kuroda, C. Hisatsune, T. Nakamura, K. Matsuo, and K. Mikoshiba. Proc. Natl. Acad. Sci. U. S. A. 105:8643, 2008), we demonstrated that osteoblasts induce osteoclast differentiation via Ca(2+) oscillation/calcineurin-dependent and -independent NFATc1 activation pathways; however, the mechanism underlying the latter remained unclear. Here we show that Cot, a serine/threonine kinase also known as tumor progression locus 2 (Tpl-2), directly phosphorylates all Ca(2+)/calcineurin-regulated NFAT family members (NFATc1 through NFATc4) and increases their protein levels. Moreover, Cot activity in osteoclasts was enhanced via cell-cell interaction with osteoblasts, and Cot promoted Ca(2+) oscillation/calcineurin-independent osteoclastogenesis by increasing NFATc1 stability through phosphorylation. We propose that NFAT activation in vivo occurs via phosphorylation-induced protein stabilization, even in the absence of Ca(2+) oscillation and calcineurin activity.
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