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Regulation of bad phosphorylation and association with Bcl-x(L) by the MAPK/Erk kinase

M P Scheid1, K M Schubert, V Duronio

  • 1Jack Bell Research Centre, University of British Columbia, Vancouver, British Columbia V6H 3Z6, Canada.

The Journal of Biological Chemistry
|October 16, 1999
PubMed

Insights

Growth factor receptor signaling prevents apoptosis by phosphorylating the Bad protein. This study reveals the Ras-MAPK pathway

Area of Science:

  • Cellular signaling pathways
  • Apoptosis regulation
  • Protein phosphorylation

Background:

  • The Bcl-2 family protein Bad plays a crucial role in apoptosis.
  • Growth factor receptors initiate survival signals that can inhibit apoptosis.
  • The precise mechanisms linking survival signaling to Bad regulation are under investigation.

Purpose of the Study:

  • To investigate the role of cytokine stimulation in Bad phosphorylation.
  • To identify the specific signaling pathways involved in Bad phosphorylation.
  • To determine the functional consequences of Bad phosphorylation on its interaction with Bcl-x(L).

Main Methods:

  • Cytokine stimulation of cells.
  • Analysis of Bad protein phosphorylation at specific residues (serine 112 and serine 136).
  • Investigation of the involvement of the MEK (Mitogen-activated protein kinase kinase) and Ras-MAPK (Ras-Mitogen-activated protein kinase) pathways.
  • Assessment of Bad and Bcl-x(L) protein interactions.

Main Results:

  • Cytokine stimulation induced Bad phosphorylation at serine 112 in a MEK-dependent manner.
  • Phosphorylation occurred at additional sites distinct from serine 112.
  • Phosphorylation at serine 136, previously linked to protein kinase B/Akt, was not detected.
  • Phosphorylation of serine 112 was essential for the dissociation of Bad from Bcl-x(L).

Conclusions:

  • The Ras-MAPK pathway is involved in the phosphorylation of Bad in mammalian cells.
  • MEK-dependent phosphorylation of serine 112 is critical for regulating Bad's interaction with Bcl-x(L).
  • This study elucidates a novel mechanism linking growth factor signaling to apoptosis prevention via Bad regulation.

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