Trial reportThe American journal of pathology2007
Central role of protein kinase Cepsilon in constitutive activation of ERK1/2 and Rac1 in the malignant cells of hairy cell leukemia.
Trial report in The American journal of pathology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
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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
14 citing papers in PubMed, 28 citations in OpenAlex.
- Hairy cell leukemia: a chronic B-cell lymphoma with unique clinicopathological features and unresolved molecular mechanisms.Blood advances · 2026Review
- Protein Kinase C Epsilon Overexpression Is Associated With Poor Patient Outcomes in AML and Promotes Daunorubicin Resistance Through p-Glycoprotein-Mediated Drug Efflux.Frontiers in oncology · 2022Article
- Distinctive requirement of PKCε in the control of Rho GTPases in epithelial and mesenchymally transformed lung cancer cells.Oncogene · 2019Article
- Rac GTPases in Hematological Malignancies.International journal of molecular sciences · 2018Review
- The role of Rac in tumor susceptibility and disease progression: from biochemistry to the clinic.Biochemical Society transactions · 2018Review
- Protein kinase Cɛ inhibition restores megakaryocytic differentiation of hematopoietic progenitors from primary myelofibrosis patients.Leukemia · 2015Article
- Clinical observations on chemotherapy curable malignancies: unique genetic events, frozen development and enduring apoptotic potential.BMC cancer · 2015Article
- HepaCAM inhibits clear cell renal carcinoma 786-0 cell proliferation via blocking PKCε translocation from cytoplasm to plasma membrane.Molecular and cellular biochemistry · 2014Article
- Variant B cell receptor isotype functions differ in hairy cell leukemia with mutated BRAF and IGHV genes.PloS one · 2014Article
- Role of calcium-dependent protein kinases in chronic myeloid leukemia: combined effects of PKC and BCR-ABL signaling on cellular alterations during leukemia development.OncoTargets and therapy · 2014Review
- Proteins kinase Cɛ is required for non-small cell lung carcinoma growth and regulates the expression of apoptotic genes.Oncogene · 2012Article
- BRAF mutations in hairy-cell leukemia.The New England journal of medicine · 2011Article
- Role for PKC δ in Fenretinide-Mediated Apoptosis in Lymphoid Leukemia Cells.Journal of signal transduction · 2010Article
- A novel quinoline, MT477: suppresses cell signaling through Ras molecular pathway, inhibits PKC activity, and demonstrates in vivo anti-tumor activity against human carcinoma cell lines.Investigational new drugs · 2008Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We have previously identified the presence of Ras/Raf-independent constitutive activation of extracellular signal-regulated kinase (ERK) in the hairy cells (HCs) of hairy cell leukemia. The aim of the present study was to characterize the signaling components involved in this activation and their relationship to the reported activation of Rac1. We found that both Rac1 and ERK activation in HCs are downstream of active Src and protein kinase C (PKC). Inhibition with toxin B showed that Rac1 plays no role in ERK activation in HCs. However, toxin B inhibited p60src and the Rac1-GEF Vav, demonstrating a positive feedback/activation of p60src by Rac1. Treatment with specific small interfering RNA for various PKC isoforms, or with PKC isoform-specific inhibitors, demonstrated a central role for PKCepsilon in the constitutive activation of Rac1 and ERK in HCs. PKCepsilon and active ERK were mutually associated and co-localized with mitochondria in HCs. Furthermore, active PKCepsilon was nitrated on tyrosine, pointing to a reactive oxygen species-dependent mechanism of activation. By being involved in activation of ERK and Rac1, PKCepsilon plays roles in both the survival of HCs and in the cytoskeletal dynamics responsible for the distinctive morphology and tissue homing of these cells. Our study therefore describes novel aspects of signaling important for the pathogenesis of hairy cell leukemia.
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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.