ArticleThe Journal of clinical investigation1998
PYK2 in osteoclasts is an adhesion kinase, localized in the sealing zone, activated by ligation of alpha(v)beta3 integrin, and phosphorylated by src kinase.
Article in The Journal of clinical investigation, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
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Who cites it
80 citing papers in PubMed.
- Regulation of cAMP levels in osteocytes by mechano-sensitive focal adhesion kinase and phosphodiesterase 8A.iScience · 2026Article
- Bone matrix proteins: regulators of skeletal remodeling and repair.Journal of bone and mineral metabolism · 2026Review
- SNX10 in autosomal recessive osteosclerosis, osteosarcoma, rheumatoid arthritis, and osteoporosis: molecular mechanisms and therapeutic implications.Frontiers in cell and developmental biology · 2025Review
- CD38 Inhibitor 78c Attenuates Pro-Inflammatory Cytokine Expression and Osteoclastogenesis in Macrophages.Cells · 2024Article
- Selective Pyk2 inhibition enhances bone restoration through SCARA5-mediated bone marrow remodeling in ovariectomized mice.Cell communication and signaling : CCS · 2024Article
- Targeting PYK2, entrectinib allays anterior subcapsular cataracts in mice by regulating TGFβ2 signaling pathway.Molecular medicine (Cambridge, Mass.) · 2024Article
- Mechanotransduction in subchondral bone microenvironment and targeted interventions for osteoarthritis.Mechanobiology in medicine · 2024Review
- Article
- Activated PyK2 and Its Associated Molecules Transduce Cellular Signaling from the Cancerous Milieu for Cancer Metastasis.International journal of molecular sciences · 2022Review
- Tyrosine Kinase Src Is a Regulatory Factor of Bone Homeostasis.International journal of molecular sciences · 2022Review
- Inhibitor of protein kinase N3 suppresses excessive bone resorption in ovariectomized mice.Journal of bone and mineral metabolism · 2022Article
- Purification and Biological Function of Caldecrin.Medicines (Basel, Switzerland) · 2021Review
- The Non-receptor Tyrosine Kinase Pyk2 in Brain Function and Neurological and Psychiatric Diseases.Frontiers in synaptic neuroscience · 2021Review
- Pyk2 deficiency enhances bone mass during midpalatal suture expansion.Orthodontics & craniofacial research · 2020Article
- TASK channels: channelopathies, trafficking, and receptor-mediated inhibition.Pflugers Archiv : European journal of physiology · 2020Review
- A FAK/HDAC5 signaling axis controls osteocyte mechanotransduction.Nature communications · 2020Article
- L-Plastin deficiency produces increased trabecular bone due to attenuation of sealing ring formation and osteoclast dysfunction.Bone research · 2020Article
- [Research progress on the pathogenesis of inflammatory external root resorption].Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology · 2019Article
- Regulation of cytoskeleton and adhesion signaling in osteoclasts by tetraspanin CD82.Bone reports · 2019Article
- A dual-specific macrophage colony-stimulating factor antagonist of c-FMS and αvβ3 integrin for osteoporosis therapy.PLoS biology · 2018Article
20 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Osteoclast activation is initiated by adhesion to the bone surface, followed by cytoskeletal rearrangement, the formation of the sealing zone, and a polarized ruffled membrane. This study shows that PYK2/CAKbeta/RAFTK, a cytoplasmic kinase related to the focal adhesion kinase, is highly expressed in rat osteoclasts in vivo. Using murine osteoclast-like cells (OCLs) or their mononuclear precursors (pOCs), generated in a coculture of bone marrow and osteoblastic MB1.8 cells, we show: (a) tyrosine phosphorylation of PYK2 upon ligation of beta3 integrins or adhesion of pOCs to serum, vitronectin, osteopontin, or fibronectin but not to laminin or collagen; (b) coimmunoprecipitation of PYK2 and c-Src from OCLs; (c) PYK2 binding to the SH2 domains of Src; (d) marked reduction in tyrosine phosphorylation and kinase activity of PYK2 in OCLs derived from Src (-/-) mice, which do not form actin rings and do not resorb bone; (e) PYK2 phosphorylation by exogeneous c-Src; (f) translocation of PYK2 to the Triton X-100 insoluble cytoskeletal fraction upon adhesion; (g) localization of PYK2 in podosomes and the ring-like structures in OCLs plated on glass and in the sealing zone in OCLs plated on bone; and (h) activation of PYK2, in the presence of MB1.8 cells, parallels the formation of sealing zones and pit resorption in vitro and is reduced by echistatin or calcitonin and cytochalasin D. Taken together, these findings suggest that Src-dependent tyrosine phosphorylation of PYK2 is involved in the adhesion-induced formation of the sealing zone, required for osteoclastic bone resorption.
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