CD28 dependent PI3K/Akt signaling

Stable Identifier
R-HSA-389357
Type
Pathway
Species
Homo sapiens
ReviewStatus
5/5
Locations in the PathwayBrowser
General
SVG |   | PPTX  | SBGN
Click the image above or here to open this pathway in the Pathway Browser
CD28-mediated PI3K signaling plays a crucial role in augmenting T cell activation and survival. Phosphoinositide 3-kinases (PI3Ks) are lipid kinases that can be activated downstream of various receptors, including the T-cell receptor (TCR), co-stimulatory receptors like CD28, and cytokine or chemokine receptors. The role of PI3K signaling differs depending on the upstream receptor involved. CD28, specifically, contains a YMNM consensus motif in its cytoplasmic tail, which serves as a binding site for the p85 regulatory subunit of PI3K.
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).
Literature References
PubMed ID Title Journal Year
12670391 The PI-3 kinase/Akt pathway and T cell activation: pleiotropic pathways downstream of PIP3

Kane, LP, Weiss, A

Immunol Rev 2003
15046602 Phosphoinositide 3-kinase in T cell activation and survival

Emery, JL, Vanhaesebroeck, B, Bilancio, A, Okkenhaug, K

Biochem Soc Trans 2004
Participants
Participates
Orthologous Events
Authored
Reviewed
Created
Cite Us!