ArticleJournal of immunology (Baltimore, Md. : 1950)2009
SLP-76 couples Syk to the osteoclast cytoskeleton.
Article in Journal of immunology (Baltimore, Md. : 1950), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
22 citing papers in PubMed, 39 citations in OpenAlex.
- Purification and Biological Function of Caldecrin.Medicines (Basel, Switzerland) · 2021Review
- Article
- Oleoylethanolamide Exhibits GPR119-Dependent Inhibition of Osteoclast Function and GPR119-Independent Promotion of Osteoclast Apoptosis.Molecules and cells · 2020Article
- Expression of typical osteoclast markers by PBMCs after PEG-induced fusion as a model for studying osteoclast differentiation.Journal of molecular histology · 2017Article
- Regulation of Embryonic and Postnatal Development by the CSF-1 Receptor.Current topics in developmental biology · 2017Review
- SLP76 integrates into the B-cell receptor signaling cascade in chronic lymphocytic leukemia cells and is associated with an aggressive disease course.Haematologica · 2016Article
- Targeting Syk in Autoimmune Rheumatic Diseases.Frontiers in immunology · 2016Review
- Zap70 inhibits Syk-mediated osteoclast function.Journal of cellular biochemistry · 2013Article
- Osteoclasts: New Insights.Bone research · 2013Review
- Talin1 and Rap1 are critical for osteoclast function.Molecular and cellular biology · 2013Article
- Negative regulation of osteoclast precursor differentiation by CD11b and β2 integrin-B-cell lymphoma 6 signaling.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2013Article
- Spleen tyrosine kinase (Syk) is a potent target for GvHD prevention at different cellular levels.Leukemia · 2012Article
- c-Src links a RANK/αvβ3 integrin complex to the osteoclast cytoskeleton.Molecular and cellular biology · 2012Article
- Serum calcium-decreasing factor, caldecrin, inhibits receptor activator of NF-κB ligand (RANKL)-mediated Ca2+ signaling and actin ring formation in mature osteoclasts via suppression of Src signaling pathway.The Journal of biological chemistry · 2012Article
- Src inhibitors in the treatment of metastatic bone disease: rationale and clinical data.Clinical investigation · 2011Article
- Rac deletion in osteoclasts causes severe osteopetrosis.Journal of cell science · 2011Article
- 3BP2-deficient mice are osteoporotic with impaired osteoblast and osteoclast functions.The Journal of clinical investigation · 2011Article
- Fyn promotes proliferation, differentiation, survival and function of osteoclast lineage cells.Journal of cellular biochemistry · 2010Article
- Cytoskeletal dysfunction dominates in DAP12-deficient osteoclasts.Journal of cell science · 2010Article
- Microfibril-associated glycoprotein-1, an extracellular matrix regulator of bone remodeling.The Journal of biological chemistry · 2010Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The capacity of the osteoclast (OC) to resorb bone is dictated by cytoskeletal organization, which in turn emanates from signals derived from the alpha(v)beta(3) integrin and c-Fms. Syk is key to these signals and, in other cells, this tyrosine kinase exerts its effects via intermediaries including the SLP adaptors, SLP-76 and BLNK (B cell linker). Thus, we asked whether these two SLP proteins regulate OC function. We find BLNK-deficient OCs are normal, whereas cytoskeletal organization of those lacking SLP-76 is delayed, thus modestly reducing bone resorption in vitro. Cytoskeletal organization and bone resorption are more profoundly arrested in cultured OCs deficient in BLNK and SLP-76 double knockout (DKO) phenotypes. In contrast, stimulated bone resorption in vivo is inhibited approximately 40% in either SLP-76(-/-) or DKO mice. This observation, taken with the fact that DKO OCs are rescued by retroviral transduction of only SLP-76, indicates that SLP-76 is the dominant SLP family member in the resorptive process. We also find SLP-76 is phosphorylated in a Syk-dependent manner. Furthermore, in the absence of the adaptor protein, integrin-mediated phosphorylation of Vav3, the OC cytoskeleton-organizing guanine nucleotide exchange factor, is abrogated. In keeping with a central role of SLP-76/Vav3 association in osteoclastic resorption, retroviral transduction of SLP-76, in which the Vav binding site is disrupted (3YF), fails to normalize the cytoskeleton of DKO OCs and the resorptive capacity of the cells. Finally, c-Fms-activated Syk also exerts its OC cytoskeleton-organizing effect in a SLP-76/Vav3-dependent manner.
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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.