ArticleNature immunology2011
A motif in the V3 domain of the kinase PKC-θ determines its localization in the immunological synapse and functions in T cells via association with CD28.
Article in Nature immunology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers.
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Who cites it
98 citing papers in PubMed, 143 citations in OpenAlex.
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- PKC isoforms in hematopoietic lineages and myeloid/lymphoid leukemias: mechanistic insights and therapeutic prospects.Frontiers in oncology · 2026Review
- CD28-mediated linear and parallel costimulatory signaling cooperatively regulate CAR-T cell functions via CAR-CD28 microclusters.Communications biology · 2025Article
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- Reciprocal Modulation of Tumour and Immune Cell Motility: Uncovering Dynamic Interplays and Therapeutic Approaches.Cancers · 2025Review
- Molecular dynamics at immune synapse lipid rafts influence the cytolytic behavior of CAR T cells.Science advances · 2025Article
- Single-cell transcriptomics reveals pathogen interactions and T cell reprogramming in HIV andFrontiers in immunology · 2025Article
- Changing the location of proteins on the cell surface is a promising strategy for modulating T cell functions.Immunology · 2024Review
- Cancer-associated mutations in protein kinase C theta are loss-of-function.The Biochemical journal · 2024Article
- A partial human LCK defect causes a T cell immunodeficiency with intestinal inflammation.The Journal of experimental medicine · 2024Article
- Protein Kinase C at the Crossroad of Mutations, Cancer, Targeted Therapy and Immune Response.Biology · 2023Review
- Human CARMIL2 deficiency underlies a broader immunological and clinical phenotype than CD28 deficiency.The Journal of experimental medicine · 2023Article
- Distinct transcriptional signatures in purified circulating immune cells drive heterogeneity in disease location in IBD.BMJ open gastroenterology · 2023Article
- The Peptidyl-ProlylFrontiers in immunology · 2023Article
- Recent advances in understanding TCR signaling: a synaptic perspective.Faculty reviews · 2023Review
- NFκB signaling in T cell memory.Frontiers in immunology · 2023Review
- Beyond GWAS-Could Genetic Differentiation within the Allograft Rejection Pathway Shape Natural Immunity to COVID-19?International journal of molecular sciences · 2022Article
- PKCθ-mediated serine/threonine phosphorylations of FAK govern adhesion and protrusion dynamics within the lamellipodia of migrating breast cancer cells.Cancer letters · 2022Article
38 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 5 institutions in 3 countries.
Funding
Abstract
Protein kinase C-θ (PKC-θ) translocates to the center of the immunological synapse, but the underlying mechanism and its importance in T cell activation are unknown. Here we found that the V3 domain of PKC-θ was necessary and sufficient for localization to the immunological synapse mediated by association with the coreceptor CD28 and dependent on the kinase Lck. We identified a conserved proline-rich motif in V3 required for association with CD28 and immunological synapse localization. We found association with CD28 to be essential for PKC-θ-mediated downstream signaling and the differentiation of T helper type 2 cells (T(H)2 cells) and interleukin 17-producing helper T cells (T(H)17 cells) but not of T helper type 1 cells (T(H)1 cells). Ectopic expression of V3 sequestered PKC-θ from the immunological synapse and interfered with its functions. Our results identify a unique mode of CD28 signaling, establish a molecular basis for the immunological synapse localization of PKC-θ and indicate V3-based 'decoys' may be therapeutic modalities for T cell-mediated inflammatory diseases.
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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.