Pathway Human Homo sapiens

CD28 dependent PI3K/Akt signaling

R-HSA-389357 in Reactome release 97: under Co-stimulation by CD28, with 29 genes placed in it by the mapping files and 0 child pathways in the hierarchy.

The same number in the other species

Reactome writes the mouse and rat events it infers from a human pathway under the human number with the species token. A door opens only where that species' own list in this release holds the id: R-MMU-389357 (mouse), R-RNO-389357 (rat). Whether the event was inferred from this one is what the record says.

The record
The genes
Parents and children

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This page reads the pathway's record from its source while you read the rest; with scripts off the card stays at its loading line. Reload with scripts on to see it, or open the source's own page from the link in the card.

01The record

Reactome's own record of this pathway

What this tells you

The pathway list, the hierarchy and the genes on this page are read from the files Reactome publishes for Reactome release 97, built into this site on 2026-09-09: the pathway list, the hierarchy relationship file and the two gene mapping files. The record card is the one live read, Reactome's own record of this pathway.

Reactome's download page describes the mapping files: Mapping files link the source database identifier to the lowest level pathway diagram or subset of the pathway, all levels of the pathway hierarchy or database identifier to all reactions. [R13] The gene list here is the all-levels mapping of NCBI Gene ids, filled from the all-levels mapping of Ensembl ids where the NCBI file has no row for a gene; each row names which file it came from by the shape of its source id. Each row carries the evidence codes the file writes for it, as written and unranked, and both where the file writes both; no page of Reactome's documentation the survey read defines the codes, so this page does not expand them. A gene id the identity files do not name is kept as the source's own id with no door rather than turned into a symbol.

On citing what a search finds, Reactome says: It should be remembered that while we strive to contain the most current and accurate data, Reactome should not be used in citations where other primary sources of information are available. [R12] The record card prints the literature Reactome attaches to a curated pathway for that reason. The data are public domain: All data in the Reactome database and files derived from that data are licensed under the Creative Commons Public Domain Dedication (CC0). User may copy, modify, and distribute these data, even for commercial purposes, without asking for permission. Attribution is encouraged but not required. [R10] The pathway illustrations are licensed apart, under CC BY 4.0, and none is shown here.

A gene on this list is one Reactome places in this pathway in this release, and that is all the row says: it does not say the gene is expressed in a tissue or associated with a disease, which are the other two explorers' questions, read from other sources. Reactome's papers of record are [R01] [R02].

[R01] Ragueneau E, Gong C, Sinquin P, Sevilla C, Beavers D, Grentner A, et al. (2026). The Reactome Knowledgebase 2026. Nucleic Acids Research 54:D673-D681. PMID 41251150, doi 10.1093/nar/gkaf1223.
[R02] Milacic M, Beavers D, Conley P, Gong C, Gillespie M, Griss J, et al. (2024). The Reactome Pathway Knowledgebase 2024. Nucleic Acids Research 52:D672-D678. PMID 37941124, doi 10.1093/nar/gkad1025.
[R10] Reactome, reactome.org. License Agreement. https://reactome.org/license, read 2026-09-09.
[R12] Reactome, reactome.org. Citing us. https://reactome.org/cite, read 2026-09-09.
[R13] Reactome, reactome.org. Download. https://reactome.org/download-data, read 2026-09-09.

Stable id: R-HSA-389357.3
Class: Pathway
Species: Homo sapiens (human)
Inferred: no: a curated human pathway
Disease pathway: no
Released: 2009-09-30
Last updated: 2022-04-07
Events inside: 9, counted from the record

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 Reactome attaches

Phosphoinositide 3-kinase in T cell activation and survivalBiochem Soc Trans, 2004, vol. 32, p. 332-5PubMed 15046602
The PI-3 kinase/Akt pathway and T cell activation: pleiotropic pathways downstream of PIP3Immunol Rev, 2003, vol. 192, p. 7-20PubMed 12670391

Reactome's record lists 14 orthologous events, R-MMU-389357 (Mus musculus), R-RNO-389357 (Rattus norvegicus) among the species this site serves, and 12 in species this site opens no page for.

Reactome ContentService, this pathway's record · Reactome v97 · read 2026-09-30 ET · Reactome pathway browser"CD28 dependent PI3K/Akt signaling". Reactome, release 97, https://reactome.org/PathwayBrowser/#/R-HSA-389357 with StableID: R-HSA-389357.3 (accessed 2026-09-30 ET). Reactome version 97 (CC0).

Reading this pathway's record from Reactome (the pathway record).Still reading. A first read of a pathway can take a while; this page waits up to 35 seconds for it, and its scripts then bring in the panel, or a line saying what did not arrive.

02The genes

Genes Reactome places in this human pathway

The mapping files place 29 genes in this human pathway; showing 1 to 29, in pages of 100, sorted by symbol for reading. The order carries no ranking. 2 of the rows shown carry an id the identity file does not name, kept as the source wrote it.

Genes Reactome places in this human pathway, page 1 of 1
Gene	Authority id	Mapping file id	Evidence codes
GeneAKT1	AuthorityHGNC:391	Mapping file id207 NCBI file	EvidenceTAS
GeneAKT2	AuthorityHGNC:392	Mapping file id208 NCBI file	EvidenceTAS
GeneAKT3	AuthorityHGNC:393	Mapping file id10000 NCBI file	EvidenceTAS
GeneCD28	AuthorityHGNC:1653	Mapping file id940 NCBI file	EvidenceTAS
GeneCD80	AuthorityHGNC:1700	Mapping file id941 NCBI file	EvidenceTAS
GeneCD86	AuthorityHGNC:1705	Mapping file id942 NCBI file	EvidenceTAS
GeneFYN	AuthorityHGNC:4037	Mapping file id2534 NCBI file	EvidenceTAS
GeneLCK	AuthorityHGNC:6524	Mapping file id3932 NCBI file	EvidenceTAS
GeneMAP3K14	AuthorityHGNC:6853	Mapping file id9020 NCBI file	EvidenceTAS
GeneMAP3K8	AuthorityHGNC:6860	Mapping file id1326 NCBI file	EvidenceTAS
GeneMAPKAP1	AuthorityHGNC:18752	Mapping file id79109 NCBI file	EvidenceTAS
GeneMLST8	AuthorityHGNC:24825	Mapping file id64223 NCBI file	EvidenceTAS
GeneMTOR	AuthorityHGNC:3942	Mapping file id2475 NCBI file	EvidenceTAS
GenePDPK1	AuthorityHGNC:8816	Mapping file id5170 NCBI file	EvidenceTAS
GenePIK3CA	AuthorityHGNC:8975	Mapping file id5290 NCBI file	EvidenceTAS
GenePIK3CB	AuthorityHGNC:8976	Mapping file id5291 NCBI file	EvidenceTAS
GenePIK3CD	AuthorityHGNC:8977	Mapping file id5293 NCBI file	EvidenceTAS
GenePIK3CG	AuthorityHGNC:8978	Mapping file id5294 NCBI file	EvidenceTAS
GenePIK3R1	AuthorityHGNC:8979	Mapping file id5295 NCBI file	EvidenceTAS
GenePIK3R2	AuthorityHGNC:8980	Mapping file id5296 NCBI file	EvidenceTAS
GenePIK3R3	AuthorityHGNC:8981	Mapping file id8503 NCBI file	EvidenceTAS
GenePIK3R5	AuthorityHGNC:30035	Mapping file id23533 NCBI file	EvidenceTAS
GenePIK3R6	AuthorityHGNC:27101	Mapping file id146850 NCBI file	EvidenceTAS
GenePRR5	AuthorityHGNC:31682	Mapping file id55615 NCBI file	EvidenceTAS
GeneRICTOR	AuthorityHGNC:28611	Mapping file id253260 NCBI file	EvidenceTAS
GeneTHEM4	AuthorityHGNC:17947	Mapping file id117145 NCBI file	EvidenceTAS
GeneTRIB3	AuthorityHGNC:16228	Mapping file id57761 NCBI file	EvidenceTAS
Geneno symbol in the identity file	Authoritynone	Mapping file id43740571 NCBI file	EvidenceTAS
Geneno symbol in the identity file	Authoritynone	Mapping file id43740575 NCBI file	EvidenceTAS

Evidence codes on this page: TAS, as the mapping file writes them; a row carrying two was written twice by the file, once under each. The mapping file id says which file placed the gene: an NCBI Gene id from NCBI2Reactome_All_Levels.txt, an Ensembl gene id from Ensembl2Reactome_All_Levels.txt. The two files can disagree about a code, so a row's codes are the one file's view. Measured by this site's build over this release on 2026-09-09: of the 138,908 human pathway-gene pairs both files place, 207 (0.149 per cent, over 47 genes) carry TAS in the Ensembl file where the NCBI rows carry IEA alone.

Reactome mapping files, the human rows for this pathway · Reactome release 97 · read 2026-09-09 · Reactome downloads"NCBI2Reactome_All_Levels.txt" and "Ensembl2Reactome_All_Levels.txt", Reactome, release 97, https://reactome.org/download-data/ (date of access 2026-09-09). Data CC0; attribution encouraged.

03The hierarchy

Parents and children in this release's hierarchy

Parents

Co-stimulation by CD28R-HSA-38935650 genes

Children

None: no pathway of this release's list names this one as a parent.

Reactome's hierarchy is a graph rather than a tree: a pathway can sit under more than one parent, and the gene counts are each pathway's own placements at every level under it, so a parent's count is not the sum of its children's.

Reactome, the human pathway list and hierarchy relationship file · Reactome release 97 · read 2026-09-09 · Reactome downloads"ReactomePathways.txt" and "ReactomePathwaysRelation.txt", Reactome, release 97, https://reactome.org/download-data/ (date of access 2026-09-09). Data CC0; attribution encouraged.