Mol Cell Biol 1995,
PMID: 7760801
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
Document information provided by NCBI PubMed
Text Mining Data
Dashed line = No text mining data
Manually curated Databases
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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
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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