Display Settings:

Format

Send to:

Choose Destination
J Biol Chem. 1998 Apr 24;273(17):10792-7.

The activation of p38 and apoptosis by the inhibition of Erk is antagonized by the phosphoinositide 3-kinase/Akt pathway.

Author information

  • 1Laboratorio Glaxo Wellcome-Consejo Superior de Investigaciones Científicas de Biología Molecular y Celular, Centro de Biología Molecular "Severo Ochoa" (Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid), Spain.

Erratum in

  • J Biol Chem 1998 Jun 26;273(26):16630.

Abstract

Considerable attention has recently been focused on the role played by different kinase cascades in the control of apoptosis. The triggering of stress-activated kinases concomitant with the inhibition of the extracellular signal-regulated kinase (ERK) pathway has been observed in a number of cell systems undergoing programmed cell death. In addition, the activation of the phosphoinositide 3-kinase (PI 3-kinase)-Akt signaling cascade has been shown to protect from apoptosis. Here we have explored the potential role played by the inhibition of ERK in the activation of the stress kinases as well as the possible cross-talk with the PI 3-kinase pathway in HeLa cells. We show that the simple inhibition of ERK basal activity is sufficient to trigger apoptosis and p38 activation with no changes in Jun N-terminal kinase/stress-activated protein kinase. This is a process dependent on the caspases and is completely abrogated by serum. The incubation with wortmannin or the transfection of dominant negative mutants of p85 or Akt block the inhibitory function of serum, suggesting the involvement of the PI 3-kinase-Akt system. Consistent with this, expression of active mutants of PI 3-kinase and Akt inhibits p38 activation and apoptosis. We also show here that the inhibition of ERK triggers the caspase system, which is abolished by serum in a wortmannin-dependent manner. Collectively, these results demonstrate a link between ERK and the p38 apoptotic pathway that is modulated by the survival PI 3-kinase-Akt module, acting upstream the caspase system.

PMID:
9553146
[PubMed - indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for HighWire
    Loading ...
    Write to the Help Desk