Immunity 1997,
PMID: 9390691
Brennan, P; Babbage, J W; Burgering, B M; Groner, B; Reif, K; Cantrell, D A
Cell cycle progression initiated by interleukin-2 (IL-2) in T cells is critical for lymphoproliferation and an immune response. Phosphatidyl inositol 3-kinase (PI3K) is activated by IL-2. However, nuclear targets for PI3K are not known. Here we identify the cell cycle regulator E2F as an IL-2 target in T lymphocytes and PI3K as the critical signaling pathway. We eliminate both Stat5 and Raf/MEK pathways from E2F regulation. Protein kinase B (PKB) is activated by IL-2 via PI3K. The expression of an active PKB is sufficient to induce E2F activity. Inhibition of PI3K inhibits phosphorylation of Rb, induction of cyclin D3, and degradation of p27kip1. These results establish a crucial PI3K/PKB-mediated link between the IL-2 teceptor and the cell cycle machinery.
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Text Mining Data
Phosphatidyl inositol 3-kinase (PI3K) → IL-2: "
Phosphatidyl inositol 3-kinase (PI3K) is
activated by
IL-2
"
Protein kinase B (PKB) → IL-2: "
Protein kinase B (PKB) is activated by IL-2 via PI3K
"
E2F → PKB: "
The expression of an active PKB is sufficient to induce E2F activity
"
cyclin D3 → PI3K: "
Inhibition of PI3K inhibits phosphorylation of Rb, induction of cyclin D3 , and degradation of p27kip1
"
p27kip1 → PI3K: "
Inhibition of PI3K inhibits phosphorylation of Rb, induction of cyclin D3, and degradation of p27kip1
"
p27kip1 → PI3K: "
Inhibition of PI3K inhibits phosphorylation of Rb, induction of cyclin D3, and degradation of p27kip1
"
Manually curated Databases
-
NCI Pathway Database IL2 signaling events mediated by STAT5:
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GRB2/SOS1/GAB2/SHP2/PI3K complex (IL2RA-IL2RB-IL2RG-IL2-JAK1-LCK-JAK3-SHC1-GRB2-SOS1-GAB2-PTPN11-PIK3CA-PIK3R1)
→
STAT5 (dimer)-active (STAT5B/STAT5A)
(transcription, activates)
Evidence: mutant phenotype, other species
In total, 119 gene pairs are associated to this article in curated databases