Pantothenate kinase 4 controls lipid synthesis for T-cell proliferation by modulating coenzyme A and glutaminolysis.

ABSTRACT: During T-cell-mediated inflammatory responses, T cells are activated upon recognizing specific antigens presented by antigen-presenting cells. This recognition initiates signaling through the TCR and CD28, leading to their activation and subsequent clonal expansion. Within the signaling cascades triggered by TCR and CD28 engagement, the CD28-PI3K pathway serves as a central regulator of metabolic reprogramming in T cells, supporting the biosynthetic needs essential for their effective proliferation. In this study, we found that the regulation of PANK4 plays a role in TCR/CD28-mediated CD4⁺ T-cell proliferation by regulating de novo lipid synthesis. The CD28 signaling pathway negatively regulates PANK4 through direct binding with PDK1, thereby controlling de novo lipid synthesis

SUBMITTER: Hwang JR 

PROVIDER: S-EPMC12443970 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature