ArticleJournal of cellular biochemistry2014
Loss of Cbl-PI3K interaction enhances osteoclast survival due to p21-Ras mediated PI3K activation independent of Cbl-b.
Article in Journal of cellular biochemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 28 citations in OpenAlex.
- Application and translational research of magnesium in nursing care of orthopedic diseases: from mechanism to clinical translation.Frontiers in chemistry · 2026Review
- Impaired MC3T3-E1 osteoblast differentiation triggered by oncogenic HRAS is rescued by the farnesyltransferase inhibitor Tipifarnib.Scientific reports · 2025Article
- Wnt-associated adult stem cell marker Lgr6 is required for osteogenesis and fracture healing.Bone · 2023Article
- Exploring the Mechanisms of Modified Bu-Shen-Yi-Qi Decoction for COPD-Related Osteoporosis Therapy via Transcriptomics and Network Pharmacology Approach.Drug design, development and therapy · 2023Article
- Development of degradable magnesium-based metal implants and their function in promoting bone metabolism (A review).Journal of orthopaedic translation · 2022Review
- Exploring the relationship between osteoporosis and polycystic ovary syndrome based on bioinformatics.Medicine · 2022Article
- Mechanism and Experimental Verification ofFrontiers in endocrinology · 2022Article
- E3 ubiquitin ligase Casitas B lineage lymphoma-b and its potential therapeutic implications for immunotherapy.Clinical and experimental immunology · 2021Review
- Crosstalk of the Caspase Family and Mammalian Target of Rapamycin Signaling.International journal of molecular sciences · 2021Review
- Article
- PI3K activation increases SDF-1 production and number of osteoclast precursors, and enhances SDF-1-mediated osteoclast precursor migration.Bone reports · 2019Article
- A PDGFRβ-PI3K signaling axis mediates periosteal cell activation during fracture healing.PloS one · 2019Article
- The Hajdu Cheney Mutation Is a Determinant of B-Cell Allocation of the Splenic Marginal Zone.The American journal of pathology · 2018Article
- Article
- miR-216a rescues dexamethasone suppression of osteogenesis, promotes osteoblast differentiation and enhances bone formation, by regulating c-Cbl-mediated PI3K/AKT pathway.Cell death and differentiation · 2015Article
- Role of Cbl-PI3K Interaction during Skeletal Remodeling in a Murine Model of Bone Repair.PloS one · 2015Article
- Modulation of Immune Cell Functions by the E3 Ligase Cbl-b.Frontiers in oncology · 2015Review
- Loss of Cbl-PI3K interaction in mice prevents significant bone loss following ovariectomy.Bone · 2014Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Cbl family proteins, Cbl and Cbl-b, are E3 ubiquitin ligases and adaptor proteins, which play important roles in bone-resorbing osteoclasts. Loss of Cbl in mice decreases osteoclast migration, resulting in delayed bone development where as absence of Cbl-b decreases bone volume due to hyper-resorptive osteoclasts. A major structural difference between Cbl and Cbl-b is tyrosine 737 (in YEAM motif) only on Cbl, which upon phosphorylation interacts with the p85 subunit of phosphatidylinositol-3 Kinase (PI3K). In contrast to Cbl(-/-) and Cbl-b(-/-) , mice lacking Cbl-PI3K interaction due to a Y737F (tyrosine to phenylalanine, YF) mutation showed enhanced osteoclast survival, but defective bone resorption. To investigate whether Cbl-PI3K interaction contributes to distinct roles of Cbl and Cbl-b in osteoclasts, mice bearing CblY737F mutation in the Cbl-b(-/-) background (YF/YF;Cbl-b(-/-) ) were generated. The differentiation and survival were augmented similarly in YF/YF and YF/YF;Cbl-b(-/-) osteoclasts, associated with enhanced PI3K signaling suggesting an exclusive role of Cbl-PI3K interaction, independent of Cbl-b. In addition to PI3K, the small GTPase Ras also regulates osteoclast survival. In the absence of Cbl-PI3K interaction, increased Ras GTPase activity and Ras-PI3K binding were observed and inhibition of Ras activation attenuated PI3K mediated osteoclast survival. In contrast to differentiation and survival, increased osteoclast activity observed in Cbl-b(-/-) mice persisted even after introduction of the resorption-defective YF mutation in YF/YF;Cbl-b(-/-) mice. Hence, Cbl and Cbl-b play mutually exclusive roles in osteoclasts. Whereas Cbl-PI3K interaction regulates differentiation and survival, bone resorption is predominantly regulated by Cbl-b in osteoclasts.
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