ArticleJournal of immunology (Baltimore, Md. : 1950)2008
Protein kinase C-theta is required for efficient positive selection.
Article in Journal of immunology (Baltimore, Md. : 1950), 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 27 citations in OpenAlex.
- PKC isoforms in hematopoietic lineages and myeloid/lymphoid leukemias: mechanistic insights and therapeutic prospects.Frontiers in oncology · 2026Review
- Article
- Novel Mouse Model Reveals That Serine Phosphorylation of L-Plastin Is Essential for Effective Splenic Clearance of Pneumococcus.Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- Loss-of-function phenotype of a PKCθCell communication and signaling : CCS · 2019Article
- Novel mutant mouse line emphasizes the importance of protein kinase C theta for CD4Cell communication and signaling : CCS · 2019Article
- Protein kinase C theta is required for efficient induction of IL-10-secreting T cells.PloS one · 2017Article
- Gene targeting RhoA reveals its essential role in coordinating mitochondrial function and thymocyte development.Journal of immunology (Baltimore, Md. : 1950) · 2014Article
- Protein kinase C inhibitors for immune disorders.Drug discovery today · 2014Review
- Significant involvement of nuclear factor-κB-inducing kinase in proper differentiation of αβ and γδ T cells.Immunology · 2014Article
- PKCθ/β and CYLD are antagonistic partners in the NFκB and NFAT transactivation pathways in primary mouse CD3+ T lymphocytes.PloS one · 2013Article
- Regulation of Lipid Signaling by Diacylglycerol Kinases during T Cell Development and Function.Frontiers in immunology · 2013Article
- The yin and yang of protein kinase C-theta (PKCθ): a novel drug target for selective immunosuppression.Advances in pharmacology (San Diego, Calif.) · 2013Review
- The role of protein kinase cη in T cell biology.Frontiers in immunology · 2012Article
- Involvement of distinct PKC gene products in T cell functions.Frontiers in immunology · 2012Article
- Protein kinase C η is required for T cell activation and homeostatic proliferation.Science signaling · 2011Article
- Regulation and Function of the RasGRP Family of Ras Activators in Blood Cells.Genes & cancer · 2011Article
- Lipid signaling in T-cell development and function.Cold Spring Harbor perspectives in biology · 2010Review
- PKCtheta is necessary for efficient activation of NFkappaB, NFAT, and AP-1 during positive selection of thymocytes.Immunology letters · 2010Article
- Protein kinase C regulates mitochondrial targeting of Nur77 and its family member Nor-1 in thymocytes undergoing apoptosis.European journal of immunology · 2010Article
- Roles of the NF-kappaB pathway in lymphocyte development and function.Cold Spring Harbor perspectives in biology · 2010Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Protein kinase C-theta (PKCtheta) is critical for TCR-initiated signaling in mature T cells, but initial reports found no requirement for PKCtheta in thymocyte development. Thymocytes and peripheral T cells utilize many of the same signaling components and, given the significant role of PKCtheta in peripheral T cells, it was surprising that it was not involved at all in TCR signaling in thymocytes. We decided to re-evaluate the role of PKCtheta in thymocyte development using the well-characterized class II-restricted n3.L2 TCR-transgenic TCR model. Analysis of n3.L2 PKCtheta(-/-) mice revealed a defect in thymocyte-positive selection, resulting in a 50% reduction in the generation of n3.L2 CD4 single-positive thymocytes and n3.L2 CD4 mature T cells. Competition between n3.L2 WT and n3.L2 PKCtheta(-/-) thymocytes in bone marrow chimeras revealed a more dramatic defect, with a >80% reduction in generation of n3.L2 CD4 single-positive thymocytes derived from PKCtheta(-/-) mice. Inefficient positive selection of n3.L2 PKCtheta(-/-) CD4 single-positive cells resulted from "weaker" signaling through the TCR and correlated with diminished ERK activation. The defect in positive selection was not complete in the PKCtheta(-/-) mice, most likely accounted for by compensation by other PKC isoforms not evident in peripheral cells. Similar decreased positive selection of both CD4 and CD8 single-positive thymocytes was also seen in nontransgenic PKCtheta(-/-) mice. These findings now place PKCtheta as a key signaling molecule in the positive selection of thymocytes as well as in the activation of mature T cells.
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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.