ArticleCellular and molecular life sciences : CMLS2013
TULA-2, a novel histidine phosphatase, regulates bone remodeling by modulating osteoclast function.
Article in Cellular and molecular life sciences : CMLS, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 32 citations in OpenAlex.
- Decoding protein N-phosphorylation functionality and sequence patterns.Briefings in bioinformatics · 2025Article
- Investigating the role of UBASH3B in cancer: structural relevance, physiological functions, and therapeutic possibilities.Journal of experimental & clinical cancer research : CR · 2025Review
- Exploring UBASH3A: from immune regulation to autoimmune diseases.Journal of translational medicine · 2025Review
- Innate immune cell barrier-related genes inform precision prognosis in pancreatic cancer.Frontiers in immunology · 2025Article
- Mechanotransduction in subchondral bone microenvironment and targeted interventions for osteoarthritis.Mechanobiology in medicine · 2024Review
- [Role of Piezo mechanosensitive ion channels in the osteoarticular system].Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery · 2024Review
- TULA Proteins in Men, Mice, Hens, and Lice: Welcome to the Family.International journal of molecular sciences · 2023Review
- The Emerging Role of Protein Phosphatase in Regeneration.Life (Basel, Switzerland) · 2023Review
- The Sts Proteins: Modulators of Host Immunity.International journal of molecular sciences · 2023Review
- TULA-Family Regulators of Platelet Activation.International journal of molecular sciences · 2022Review
- Piezo Channels: Awesome Mechanosensitive Structures in Cellular Mechanotransduction and Their Role in Bone.International journal of molecular sciences · 2021Review
- Review
- miR-25-3p promotes endothelial cell angiogenesis in aging mice via TULA-2/SYK/VEGFR-2 downregulation.Aging · 2020Article
- NME/NM23/NDPK and Histidine Phosphorylation.International journal of molecular sciences · 2020Review
- A longitudinal characterization of sex-specific somatosensory and spatial memory deficits in HIV Tg26 heterozygous mice.PloS one · 2020Article
- Global urinary metabolic profiling of the osteonecrosis of the femoral head based on UPLC-QTOF/MS.Metabolomics : Official journal of the Metabolomic Society · 2019Article
- TULA-2 Deficiency Enhances Platelet Functional Responses to CLEC-2 Agonists.TH open : companion journal to thrombosis and haemostasis · 2018Article
- Advances in development of new tools for the study of phosphohistidine.Laboratory investigation; a journal of technical methods and pathology · 2018Review
- Histidine kinases and the missing phosphoproteome from prokaryotes to eukaryotes.Laboratory investigation; a journal of technical methods and pathology · 2018Review
- pHisphorylation: the emergence of histidine phosphorylation as a reversible regulatory modification.Current opinion in cell biology · 2017Review
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Bone is a dynamic tissue that depends on the intricate relationship between protein tyrosine kinases (PTK) and protein tyrosine phosphatases (PTP) for maintaining homeostasis. PTKs and PTPs act like molecular on and off switches and help modulate differentiation and the attachment of osteoclasts to bone matrix regulating bone resorption. The protein T cell ubiquitin ligand-2 (TULA-2), which is abundantly expressed in osteoclasts, is a novel histidine phosphatase. Our results show that of the two family members, only TULA-2 is expressed in osteoclasts and that its expression is sustained throughout the course of osteoclast differentiation, suggesting that TULA-2 may play a role during early as well late stages of osteoclast differentiation. Skeletal analysis of mice that do not express TULA or TULA-2 proteins (DKO mice) revealed that there was a decrease in bone volume due to increased osteoclast numbers and function. Furthermore, in vitro experiments indicated that bone marrow precursor cells from DKO mice have an increased potential to form osteoclasts. At the molecular level, the absence of TULA-2 in osteoclasts results in increased Syk phosphorylation at the Y352 and Y525/526 residues and activation of phospholipase C gamma 2 (PLCγ2) upon engagement of immune-receptor-tyrosine-based-activation-motif (ITAM)-mediated signaling. Furthermore, expression of a phosphatase-dead TULA-2 leads to increased osteoclast function. Taken together, these results suggest that TULA-2 negatively regulates osteoclast differentiation and function.
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Registered trials
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