ArticleMolecular cancer therapeutics2009
The Pyk2 FERM domain as a target to inhibit glioma migration.
Article in Molecular cancer therapeutics, 2009. 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, 26 citations in OpenAlex.
- Window of opportunity study measuring defactinib and avutometinib delivery in glioblastomas.Cancer chemotherapy and pharmacology · 2026Article
- Review
- EGFRvIII Confers Sensitivity to Saracatinib in a STAT5-Dependent Manner in Glioblastoma.International journal of molecular sciences · 2024Article
- Pyk2/FAK Signaling Is Upregulated in Recurrent Glioblastoma Tumors in a C57BL/6/GL261 Glioma Implantation Model.International journal of molecular sciences · 2023Article
- Microglial Cytokines Induce Invasiveness and Proliferation of Human Glioblastoma through Pyk2 and FAK Activation.Cancers · 2021Article
- TROY signals through JAK1-STAT3 to promote glioblastoma cell migration and resistance.Neoplasia (New York, N.Y.) · 2020Article
- Role of Pyk2 in Human Cancers.Medical science monitor : international medical journal of experimental and clinical research · 2018Review
- Review
- A Novel Signaling Complex between TROY and EGFR Mediates Glioblastoma Cell Invasion.Molecular cancer research : MCR · 2018Article
- Article
- Article
- Proliferation and migration of tumor cells in tapered channels.Biomedical microdevices · 2013Article
- TROY (TNFRSF19) promotes glioblastoma survival signaling and therapeutic resistance.Molecular cancer research : MCR · 2013Article
- A Novel Interaction between Pyk2 and MAP4K4 Is Integrated with Glioma Cell Migration.Journal of signal transduction · 2013Article
- Reciprocal activation of transcription factors underlies the dichotomy between proliferation and invasion of glioma cells.PloS one · 2013Article
- Dynamin and PTP-PEST cooperatively regulate Pyk2 dephosphorylation in osteoclasts.The international journal of biochemistry & cell biology · 2012Article
- Inhibition of Pyk2 blocks lung inflammation and injury in a mouse model of acute lung injury.Respiratory research · 2012Article
- Extracellular ATP stimulates epithelial cell motility through Pyk2-mediated activation of the EGF receptor.Cellular signalling · 2011Article
- The Pyk2 FERM regulates Pyk2 complex formation and phosphorylation.Cellular signalling · 2011Article
- HCMV pUS28 initiates pro-migratory signaling via activation of Pyk2 kinase.Herpesviridae · 2010Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The invasion of malignant glioma cells into the surrounding normal brain precludes effective clinical treatment. In this report, we investigated the role of the NH(2)-terminal FERM domain in the regulation of the promigratory function of Pyk2. We report that the substitution of residues that constitute a small cleft on the surface of the F3 module of the FERM domain do not significantly alter Pyk2 expression but result in the loss of Pyk2 phosphorylation. A monoclonal antibody, designated 12A10, specifically targeting the Pyk2 FERM domain was generated and recognizes an epitope located on the beta5C-alpha1C surface of the F3 module of the FERM domain. Amino acid substitutions in the F3 module that resulted in the loss of Pyk2 phosphorylation also inhibited the binding of 12A10, suggesting that the 12A10 epitope overlaps a site that plays a role in Pyk2 activity. Conjugation of 12A10 to a membrane transport peptide led to intracellular accumulation and inhibition of glioma cell migration in a concentration-dependent manner. A single chain Fv fragment of 12A10 was stable when expressed in the intracellular environment, interacted directly with Pyk2, reduced Pyk2 phosphorylation, and inhibited glioma cell migration in vitro. Stable intracellular expression of the 12A10 scFv significantly extended survival in a glioma xenograft model. Together, these data substantiate a central role for the FERM domain in regulation of Pyk2 activity and identify the F3 module as a novel target to inhibit Pyk2 activity and inhibit glioma progression.
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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.