ArticleJournal of cellular physiology2009
Activation of Src kinase by protein-tyrosine phosphatase-PEST in osteoclasts: comparative analysis of the effects of bisphosphonate and protein-tyrosine phosphatase inhibitor on Src activation in vitro.
Article in Journal of cellular physiology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 41 citations in OpenAlex.
- Targeting post-translational modifications: novel insights into bone metabolic diseases.Journal of advanced research · 2026Review
- Osteoclast Methods in Protein Phosphatase Research.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Protein tyrosine phosphatases in skeletal development and diseases.Bone research · 2022Review
- Protein tyrosine phosphatase non-receptor type 12 (PTPN12), negatively regulated by miR-106a-5p, suppresses the progression of hepatocellular carcinoma.Human cell · 2022Article
- L-Plastin Phosphorylation: Possible Regulation by a TNFR1 Signaling Cascade in Osteoclasts.Cells · 2021Article
- L-Plastin deficiency produces increased trabecular bone due to attenuation of sealing ring formation and osteoclast dysfunction.Bone research · 2020Article
- The HBx-CTTN interaction promotes cell proliferation and migration of hepatocellular carcinoma via CREB1.Cell death & disease · 2019Article
- Methylsulfonylmethane increases osteogenesis and regulates the mineralization of the matrix by transglutaminase 2 in SHED cells.PloS one · 2019Article
- L-plastin phosphorylation regulates the early phase of sealing ring formation by actin bundling process in mouse osteoclasts.Experimental cell research · 2018Article
- Article
- Unravelling the Mechanism of TrkA-Induced Cell Death by Macropinocytosis in Medulloblastoma Daoy Cells.Molecular and cellular biology · 2016Article
- SRC kinase inhibition with saracatinib limits the development of osteolytic bone disease in multiple myeloma.Oncotarget · 2016Article
- Protein tyrosine phosphatases ε and α perform nonredundant roles in osteoclasts.Molecular biology of the cell · 2014Article
- Regulation of tumor cell migration by protein tyrosine phosphatase (PTP)-proline-, glutamate-, serine-,and threonine-rich sequence (PEST).Chinese journal of cancer · 2013Review
- RNA therapeutics targeting osteoclast-mediated excessive bone resorption.Advanced drug delivery reviews · 2012Review
- Podocyte Protein, Nephrin, Is a Substrate of Protein Tyrosine Phosphatase 1B.Journal of signal transduction · 2011Article
- Regulation of sealing ring formation by L-plastin and cortactin in osteoclasts.The Journal of biological chemistry · 2010Article
- PTP-PEST controls motility, adherens junction assembly, and Rho GTPase activity in colon cancer cells.American journal of physiology. Cell physiology · 2010Article
- Protein tyrosine phosphatase epsilon regulates integrin-mediated podosome stability in osteoclasts by activating Src.Molecular biology of the cell · 2009Article
- Spatiotemporal regulation of Src and its substrates at invadosomes.European journal of cell biologyReview
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
PTP-PEST is involved in the regulation of sealing ring formation in osteoclasts. In this article, we have shown a regulatory role for PTP-PEST on dephosphorylation of c-Src at Y527 and phosphorylation at Y418 in the catalytic site. Activation of Src in osteoclasts by over-expression of PTP-PEST resulted in the phosphorylation of cortactin at Y421 and WASP at Y294. Also enhanced as a result, is the interaction of Src, cortactin, and Arp2 with WASP. Moreover, the number of osteoclasts displaying sealing ring and bone resorbing activity was increased in response to PTP-PEST over-expression as compared with control osteoclasts. Cells expressing constitutively active-Src (527YDeltaF) simulate the effects mediated by PTP-PEST. Treatment of osteoclasts with a bisphosphonate alendronate or a potent PTP inhibitor PAO decreased the activity and phosphorylation of Src at Y418 due to reduced dephosphorylation state at Y527. Therefore, Src-mediated phosphorylation of cortactin and WASP as well as the formation of WASP.cortactin.Arp2 complex and sealing ring were reduced in these osteoclasts. Similar effects were observed in osteoclasts treated with an Src inhibitor PP2. We have shown that bisphosphonates could modulate the function of osteoclasts by inhibiting downstream signaling mediated by PTP-PEST/Src, in addition to its effect on the inhibition of the post-translational modification of small GTP-binding proteins such as Rab, Rho, and Rac as shown by others. The promising effects of the inhibitors PP2 and PAO on osteoclast function suggest a therapeutic approach for patients with bone metastases and osteoporosis as an alternative to bisphosphonates.
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