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CD28 dependent PI3K/Akt signaling
Stable Identifier
R-HSA-389357
Type
Pathway
Species
Homo sapiens
ReviewStatus
5/5
Locations in the PathwayBrowser
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Immune System (Homo sapiens)
Adaptive Immune System (Homo sapiens)
Regulation of T cell activation by CD28 family (Homo sapiens)
Co-stimulation by CD28 (Homo sapiens)
CD28 dependent PI3K/Akt signaling (Homo sapiens)
General
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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
Events
PI3K binds CD28
(Homo sapiens)
CD28 bound PI3K phosphorylates PIP2 to PIP3
(Homo sapiens)
PIP3 recruits PDPK1 to the membrane
(Homo sapiens)
PIP3 recruits AKT to the membrane
(Homo sapiens)
TORC2 (mTOR) phosphorylates AKT at S473
(Homo sapiens)
AKT binds PDPK1
(Homo sapiens)
PDPK1 phosphorylates AKT at T308
(Homo sapiens)
AKT interacts and phosphorylates Cot
(Homo sapiens)
p-S400-Cot phosphorylates NIK
(Homo sapiens)
Participates
as an event of
Co-stimulation by CD28 (Homo sapiens)
Orthologous Events
CD28 dependent PI3K/Akt signaling (Bos taurus)
CD28 dependent PI3K/Akt signaling (Caenorhabditis elegans)
CD28 dependent PI3K/Akt signaling (Canis familiaris)
CD28 dependent PI3K/Akt signaling (Danio rerio)
CD28 dependent PI3K/Akt signaling (Dictyostelium discoideum)
CD28 dependent PI3K/Akt signaling (Drosophila melanogaster)
CD28 dependent PI3K/Akt signaling (Gallus gallus)
CD28 dependent PI3K/Akt signaling (Mus musculus)
CD28 dependent PI3K/Akt signaling (Plasmodium falciparum)
CD28 dependent PI3K/Akt signaling (Rattus norvegicus)
CD28 dependent PI3K/Akt signaling (Saccharomyces cerevisiae)
CD28 dependent PI3K/Akt signaling (Schizosaccharomyces pombe)
CD28 dependent PI3K/Akt signaling (Sus scrofa)
CD28 dependent PI3K/Akt signaling (Xenopus tropicalis)
Cross References
BioModels Database
BIOMD0000000883
,
BIOMD0000000468
,
BIOMD0000000175
,
BIOMD0000000137
,
BIOMD0000000255
,
BIOMD0000000581
,
BIOMD0000000465
,
BIOMD0000000356
,
BIOMD0000000943
Authored
Garapati, P V (2008-12-16)
Reviewed
Bluestone, JA (2009-06-01)
Esensten, J (2009-06-01)
Created
Garapati, P V (2009-01-06)
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