ArticleProceedings of the National Academy of Sciences of the United States of America2017
PLCε1 regulates SDF-1α-induced lymphocyte adhesion and migration to sites of inflammation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 25 citations in OpenAlex.
- Cytokine Networks in Triple-Negative Breast Cancer: Mechanisms, Therapeutic Targets, and Emerging Strategies.Biomedicines · 2025Review
- Urbanization and genetic homogenization in the medieval Low Countries revealed through a ten-century paleogenomic study of the city of Sint-Truiden.Genome biology · 2025Article
- Osteopontin in Chronic Inflammatory Diseases: Mechanisms, Biomarker Potential, and Therapeutic Strategies.Biology · 2025Review
- Phospholipase C epsilon-1 (PLCƐ1) mediates macrophage activation and protection against tuberculosis.Infection and immunity · 2024Article
- Monomeric CXCL12-Engineered Adipose-Derived Stem Cells Transplantation for the Treatment of Ischemic Stroke.International journal of molecular sciences · 2024Article
- CXCL12-CXCR4/CXCR7 Axis in Cancer: from Mechanisms to Clinical Applications.International journal of biological sciences · 2023Review
- PLCE1 is a poor prognostic marker and may promote immune escape from osteosarcoma by the CD70-CD27 signaling pathway.Bosnian journal of basic medical sciences · 2022Article
- An irradiated marrow niche reveals a small noncollagenous protein mediator of homing, dermatopontin.Blood advances · 2021Article
- Dysregulation of DPP4-CXCL12 Balance by TGF-β1/SMAD Pathway Promotes CXCR4Journal of inflammation research · 2021Article
- In Vitro Assays to Study PD-1 Biology in Human T Cells.Current protocols in immunology · 2020Article
- The Complexity of Targeting Chemokines to Promote a Tumor Immune Response.Inflammation · 2020Review
- PLCε1 suppresses tumor growth by regulating murine T cell mobilization.Clinical and experimental immunology · 2020Article
- Conformationally active integrin endocytosis and traffic: why, where, when and how?Biochemical Society transactions · 2020Review
- Phospholipase C.Advances in experimental medicine and biology · 2020Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Regulation of integrins is critical for lymphocyte adhesion to endothelium and migration throughout the body. Inside-out signaling to integrins is mediated by the small GTPase Ras-proximate-1 (Rap1). Using an RNA-mediated interference screen, we identified phospholipase Cε 1 (PLCε1) as a crucial regulator of stromal cell-derived factor 1 alpha (SDF-1α)-induced Rap1 activation. We have shown that SDF-1α-induced activation of Rap1 is transient in comparison with the sustained level following cross-linking of the antigen receptor. We identified that PLCε1 was necessary for SDF-1α-induced adhesion using shear stress, cell morphology alterations, and crawling on intercellular adhesion molecule 1 (ICAM-1)-expressing cells. Structure-function experiments to separate the dual-enzymatic function of PLCε1 uncover necessary contributions of the CDC25, Pleckstrin homology, and Ras-associating domains, but not phospholipase activity, to this pathway. In the mouse model of delayed type hypersensitivity, we have shown an essential role for PLCε1 in T-cell migration to inflamed skin, but not for cytokine secretion and proliferation in regional lymph nodes. Our results reveal a signaling pathway where SDF-1α induces T-cell adhesion through activation of PLCε1, suggesting that PLCε1 is a specific potential target in treating conditions involving migration of T cells to inflamed organs.
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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.