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Interleukin-2 triggers a novel phosphatidylinositol 3-kinase-dependent MEK activation pathway.
- Source :
-
Molecular and cellular biology [Mol Cell Biol] 1995 Jun; Vol. 15 (6), pp. 3049-57. - Publication Year :
- 1995
-
Abstract
- 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.
- Subjects :
- Androstadienes pharmacology
Cell Cycle drug effects
Cell Line
Humans
Mitogen-Activated Protein Kinase Kinases
Phosphatidylinositol 3-Kinases
Second Messenger Systems
Signal Transduction
T-Lymphocytes metabolism
Wortmannin
Interleukin-2 metabolism
Phosphotransferases (Alcohol Group Acceptor) metabolism
Protein Kinases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0270-7306
- Volume :
- 15
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Molecular and cellular biology
- Publication Type :
- Academic Journal
- Accession number :
- 7760801
- Full Text :
- https://doi.org/10.1128/MCB.15.6.3049