Gene interactions and pathways from curated databases and text-mining
Mol Cell Biol 1995, PMID: 7760801

Interleukin-2 triggers a novel phosphatidylinositol 3-kinase-dependent MEK activation pathway.

Karnitz, L M; Burns, L A; Sutor, S L; Blenis, J; Abraham, R T

Phosphatidylinositol 3-kinase (PI3-K) has been implicated as a signal-transducing component in interleukin-2 (IL-2)-induced mitogenesis. However, the function of this lipid kinase in regulating IL-2-triggered downstream events has remained obscure. Using the potent and specific PI3-K inhibitor, wortmannin, we assessed the role of PI3-K in IL-2-mediated signaling and proliferation in the murine T-cell line CTLL-2. Addition of the drug to exponentially growing cells resulted in an accumulation of cells in the G0/G1 phase of the cell cycle. Furthermore, wortmannin also partially suppressed IL-2-induced S-phase entry in G1-synchronized cells. Analysis of IL-2-triggered signaling pathways revealed that wortmannin pretreatment resulted in complete inhibition of IL-2-provoked p70 S6 kinase activation and also attenuated IL-2-induced MAP kinase activation at drug concentrations identical to those required for inhibition of PI3-K catalytic activity. Wortmannin also diminished the IL-2-triggered activation of the MAP kinase activator, MEK, but did not inhibit activation of Raf, the canonical upstream activator of MEK. These results suggest that a novel wortmannin-sensitive activation pathway regulates MEK and MAP kinase in IL-2-stimulated T lymphocytes.

Diseases/Pathways annotated by Medline MESH: Second Messenger Systems
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Text Mining Data

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Manually curated Databases

  • NCI Pathway Database IL2-mediated signaling events: RAF1 (RAF1) → 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) (modification, activates)
    Evidence: mutant phenotype, other species
  • NCI Pathway Database IL2 signaling events mediated by PI3K: mTOR (MTOR) → p70S6K (RPS6KB1) (modification, activates)
    Evidence: mutant phenotype, other species
  • NCI Pathway Database IL2 signaling events mediated by PI3K: mTOR (MTOR) → None (modification, activates)
    Evidence: mutant phenotype, other species
  • NCI Pathway Database SHP2 signaling: RAF1 (RAF1) → 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) (modification, activates)
    Evidence: mutant phenotype
In total, 106 gene pairs are associated to this article in curated databases