ArticleThe Journal of biological chemistry2013
Prolidase directly binds and activates epidermal growth factor receptor and stimulates downstream signaling.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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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
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- Quantitative analysis of the natural history of prolidase deficiency: description of 17 families and systematic review of published cases.Genetics in medicine : official journal of the American College of Medical Genetics · 2021Pooled it
- CRISPR/Cas9-Directed PEPD Targeting Is Associated with Reduced PEPD Activity and an Exploratory p53- and Apoptosis-Related Protein Pattern in MCF7 Breast Cancer Cells.Molecules (Basel, Switzerland) · 2026Article
- Targeted dual degradation of HER2 and EGFR obliterates oncogenic signaling, overcomes therapy resistance, and inhibits metastatic lesions in HER2-positive breast cancer models.Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · 2024Article
- Smart Nanoplatforms Responding to the Tumor Microenvironment for Precise Drug Delivery in Cancer Therapy.International journal of nanomedicine · 2024Review
- Targeting Epidermal Growth Factor Receptor for Cancer Treatment: Abolishing Both Kinase-Dependent and Kinase-Independent Functions of the Receptor.Pharmacological reviews · 2023Review
- Recombinant Human Prolidase (rhPEPD) Induces Wound Healing in Experimental Model of Inflammation through Activation of EGFR Signalling in Fibroblasts.Molecules (Basel, Switzerland) · 2023Article
- Article
- Depleting receptor tyrosine kinases EGFR and HER2 overcomes resistance to EGFR inhibitors in colorectal cancer.Journal of experimental & clinical cancer research : CR · 2022Article
- Dysregulation of macrophage PEPD in obesity determines adipose tissue fibro-inflammation and insulin resistance.Nature metabolism · 2022Article
- Recombinant Prolidase Activates EGFR-Dependent Cell Growth in an Experimental Model of Inflammation in HaCaT Keratinocytes. Implication for Wound Healing.Frontiers in molecular biosciences · 2022Article
- Loss of peptidase D binding restores the tumor suppressor functions of oncogenic p53 mutants.Communications biology · 2021Article
- The root cause of drug resistance in HER2-positive breast cancer and the therapeutic approaches to overcoming the resistance.Pharmacology & therapeutics · 2021Review
- Platelet-Rich Plasma Promotes the Proliferation of Human Keratinocytes via a Progression of the Cell Cycle. A Role of Prolidase.International journal of molecular sciences · 2021Article
- Extracellular Prolidase (PEPD) Induces Anabolic Processes through EGFR, βInternational journal of molecular sciences · 2021Article
- PROLIDASE: A Review from Discovery to its Role in Health and Disease.Frontiers in molecular biosciences · 2021Review
- Prolidase Stimulates Proliferation and Migration through Activation of the PI3K/Akt/mTOR Signaling Pathway in Human Keratinocytes.International journal of molecular sciences · 2020Article
- Development of an LC-MS Targeted Metabolomics Methodology to Study Proline Metabolism in Mammalian Cell Cultures.Molecules (Basel, Switzerland) · 2020Article
- Current Understanding of the Emerging Role of Prolidase in Cellular Metabolism.International journal of molecular sciences · 2020Review
- Functional Screening of Candidate Causal Genes for Insulin Resistance in Human Preadipocytes and Adipocytes.Circulation research · 2020Article
- A recombinant human protein targeting HER2 overcomes drug resistance in HER2-positive breast cancer.Science translational medicine · 2019Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Prolidase, also known as Xaa-Pro dipeptidase or peptidase D (PEPD), is a ubiquitously expressed cytosolic enzyme that hydrolyzes dipeptides with proline or hydroxyproline at the carboxyl terminus. In this article, however, we demonstrate that PEPD directly binds to and activates epidermal growth factor receptor (EGFR), leading to stimulation of signaling proteins downstream of EGFR, and that such activity is neither cell-specific nor dependent on the enzymatic activity of PEPD. In line with the pro-survival and pro-proliferation activities of EGFR, PEPD stimulates DNA synthesis. We further show that PEPD activates EGFR only when it is present in the extracellular space, but that PEPD is released from injured cells and tissues and that such release appears to result in EGFR activation. PEPD differs from all known EGFR ligands in that it does not possess an epidermal growth factor (EGF) motif and is not synthesized as a transmembrane precursor, but PEPD binding to EGFR can be blocked by EGF. In conclusion, PEPD is a ligand of EGFR and presents a novel mechanism of EGFR activation.
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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.