ArticleJournal of cellular biochemistry2008
Pathway crosstalk between Ras/Raf and PI3K in promotion of M-CSF-induced MEK/ERK-mediated osteoclast survival.
Article in Journal of cellular biochemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 55 citations in OpenAlex.
- Integrated analysis of Corylin from Psoralea Corylifolia inhibiting osteoporosis via MAPK pathway.Scientific reports · 2025Article
- Osteoclast Activation and Inflammatory Bone Diseases: Focusing on Receptors in Osteoclasts.Journal of inflammation research · 2025Review
- The role of E3 ubiquitin ligases in bone homeostasis and related diseases.Acta pharmaceutica Sinica. B · 2023Review
- 1,3-Dibenzyl-5-Fluorouracil Prevents Ovariectomy-Induced Bone Loss by Suppressing Osteoclast Differentiation.Immune network · 2022Article
- Lonafarnib Inhibits Farnesyltransferase via Suppressing ERK Signaling Pathway to Prevent Osteoclastogenesis in Titanium Particle-Induced Osteolysis.Frontiers in pharmacology · 2022Article
- Review
- Myeloid Lineage Ablation ofInternational journal of molecular sciences · 2021Article
- DUSP6 expression is associated with osteoporosis through the regulation of osteoclast differentiation via ERK2/Smad2 signaling.Cell death & disease · 2021Article
- Signaling pathways in human osteoclasts differentiation: ERK1/2 as a key player.Molecular biology reports · 2021Article
- FASN Knockdown Inhibited Anoikis Resistance of Gastric Cancer Cells via P-ERK1/2/Bcl-xL Pathway.Gastroenterology research and practice · 2021Article
- Hdac3 regulates bone modeling by suppressing osteoclast responsiveness to RANKL.The Journal of biological chemistry · 2020Article
- Positive and negative regulators of osteoclast apoptosis.Bone reports · 2019Review
- Deficiency in the phosphatase PHLPP1 suppresses osteoclast-mediated bone resorption and enhances bone formation in mice.The Journal of biological chemistry · 2019Article
- Crosstalk analysis of dysregulated pathways in preeclampsia.Experimental and therapeutic medicine · 2019Article
- Comparative Characterization of Osteoclasts Derived From Murine Bone Marrow Macrophages and RAW 264.7 Cells Using Quantitative Proteomics.JBMR plus · 2018Article
- Naringin promotes cellular chemokine synthesis and potentiates mesenchymal stromal cell migration via the Ras signaling pathway.Experimental and therapeutic medicine · 2018Article
- PDK1 governs thromboxane generation and thrombosis in platelets by regulating activation of Raf1 in the MAPK pathway.Journal of thrombosis and haemostasis : JTH · 2018Article
- Personalized analysis of pathway aberrance induced by sevoflurane and propofol.Molecular medicine reports · 2017Article
- Identifying key genes in glaucoma based on a benchmarked dataset and the gene regulatory network.Experimental and therapeutic medicine · 2017Article
- A novel approach to select differential pathways associated with hypertrophic cardiomyopathy based on gene co‑expression analysis.Molecular medicine reports · 2017Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
While M-CSF-mediated MEK/ERK activation promotes osteoclast survival, the signaling pathway by which M-CSF activates MEK/ERK is unresolved. Functions for PI3K, Ras, and Raf have been implicated in support of osteoclast survival, although interaction between these signaling components has not been examined. Therefore, the interplay between PI3K, Ras and Raf in M-CSF-promoted MEK/ERK activation and osteoclast survival was investigated. M-CSF activates Ras to coordinate activation of PI3K and Raf/MEK/ERK, since Ras inhibition decreased PI3K activation and PI3K inhibition did not block M-CSF-mediated Ras activation. As further support for Ras-mediated signaling, constitutively active (ca) Ras promoted MEK/ERK activation and osteoclast survival, which was blocked by inhibition of PI3K or Raf. Moreover, PI3K-selective or Raf-selective caRas were only partially able to promote osteoclast survival when compared to parental caRas. We then examined whether PI3K and Raf function linearly or in parallel downstream of Ras. Expression of caPI3K increased MEK/ERK activation and promoted osteoclast survival downstream of M-CSF, supporting this hypothesis. Blocking Raf did not decrease osteoclast survival and MEK/ERK activation promoted by caPI3K. In addition, PI3K-selective Ras-mediated survival was not blocked by Raf inhibition. Taken together, our data support that Raf signaling is separate from Ras/PI3K signaling and PI3K signaling is separate from Ras/Raf signaling. These data therefore support a role for Ras in coordinate activation of PI3K and Raf acting in parallel to mediate MEK/ERK-promoted osteoclast survival induced by M-CSF.
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