ArticleMolecular and cellular biology2009
Targeted knock-in mice expressing mutations of CD28 reveal an essential pathway for costimulation.
Article in Molecular and cellular biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 79 citations in OpenAlex.
- Proline-rich tyrosine kinase 2 controls PI3-kinase activation downstream of the T cell antigen receptor in human T cells.Journal of leukocyte biology · 2015Trial
- A CARMIL2 gain-of-function mutation suffices to trigger most CD28 costimulatory functions in vivo.The Journal of experimental medicine · 2025Article
- CD28 co-stimulation: novel insights and applications in cancer immunotherapy.Nature reviews. Immunology · 2024Review
- Article
- CD8+ T cell metabolic flexibility elicited by CD28-ARS2 axis-driven alternative splicing of PKM supports antitumor immunity.Cellular & molecular immunology · 2024Article
- Fine-Tuning through Generations: Advances in Structure and Production of CAR-T Therapy.Cancers · 2023Review
- cis-B7:CD28 interactions at invaginated synaptic membranes provide CD28 co-stimulation and promote CD8Immunity · 2023Article
- Dynamics of Chromatin Accessibility During Hematopoietic Stem Cell Differentiation Into Progressively Lineage-Committed Progeny.Stem cells (Dayton, Ohio) · 2023Article
- Co-Stimulatory Receptor Signaling in CAR-T Cells.Biomolecules · 2022Review
- PDZ Proteins SCRIB and DLG1 Regulate Myeloma Cell Surface CD86 Expression, Growth, and Survival.Molecular cancer research : MCR · 2022Article
- Involvement of MicroRNA-27a-3p in the Licorice-Induced Alteration of Cd28 Expression in Mice.Genes · 2022Article
- TRAF3 in T Cells Restrains Negative Regulators of LAT to Promote TCR/CD28 Signaling.Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- CD28 Costimulatory Domain-Targeted Mutations Enhance Chimeric Antigen Receptor T-cell Function.Cancer immunology research · 2021Article
- The Expression of CD28 and Its Synergism on the Immune Response of Flounder (Frontiers in immunology · 2021Article
- B7-CD28 co-stimulation modulates central tolerance via thymic clonal deletion and Treg generation through distinct mechanisms.Nature communications · 2020Article
- Review
- T cell costimulation, checkpoint inhibitors and anti-tumor therapy.Journal of biosciences · 2020Review
- T Cell Reprogramming Against Cancer.Methods in molecular biology (Clifton, N.J.) · 2020Review
- Survival of Long-Lived Plasma Cells (LLPC): Piecing Together the Puzzle.Frontiers in immunology · 2019Review
- Preventing Lck Activation in CAR T Cells Confers Treg Resistance but Requires 4-1BB Signaling for Them to Persist and Treat Solid Tumors in Nonlymphodepleted Hosts.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Despite extensive study, the role of phosphatidylinositol 3-kinase (PI3-kinase) activation in CD28 function has been highly contentious. To definitively address this question, we generated knock-in mice expressing mutations in two critical domains of the cytoplasmic tail of CD28. Mutation of the proximal tyrosine motif interrupted PI3-kinase binding and prevented CD28-dependent phosphorylation of protein kinase B (PKB)/Akt; however, there was no detectable effect on interleukin-2 (IL-2) secretion, expression of Bcl-X(L), or on T-cell function in vivo. Furthermore, we demonstrate that signaling initiated by the C-terminal proline motif is directly responsible for tyrosine phosphorylation of phosphoinosotide-dependent kinase 1, protein kinase C theta, and glycogen synthase kinase 3beta, as well as contributing to threonine phosphorylation of PKB. T cells mutated in this domain were profoundly impaired in IL-2 secretion, and the mice had marked impairment of humoral responses as well as less severe disease manifestations in experimental allergic encephalomyelitis. These data demonstrate that the distal proline motif initiates a critical nonredundant signaling pathway, whereas direct activation of PI3-kinase by the proximal tyrosine motif of CD28 is not required for normal T-cell function.
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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.