CD28 dependent PI3K/Akt signaling

When CD28 is engaged, it promotes the recruitment of PI3K, complementing PI3K activation downstream of the TCR. This recruitment triggers the conversion of phosphatidylinositol (4,5)-bisphosphate (PIP2) to phosphatidylinositol (3,4,5)-trisphosphate (PIP3) at the plasma membrane, which serves as a docking site for multiple signaling proteins. Among these, the guanine nucleotide exchange factor VAV and the serine/threonine kinase AKT (also known as protein kinase B, PKB) are key mediators of CD28-induced costimulatory signals. PI3K activation through CD28 promotes cytokine transcription (e.g., IL-2), T cell survival via anti-apoptotic pathways, cell cycle progression, and metabolic changes necessary for T cell growth (Riha and Rudd. 2010, Miller et al. 2009, Han et al. 2012).