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

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

Research output: Contribution to journalArticlepeer-review

148 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)3049-3057
Number of pages9
JournalMolecular and cellular biology
Issue number6
StatePublished - 1995

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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