Pim-1 kinase promotes inactivation of the pro-apoptotic Bad protein by phosphorylating it on the Ser112 gatekeeper site

FEBS Lett. 2004 Jul 30;571(1-3):43-9. doi: 10.1016/j.febslet.2004.06.050.

Abstract

Constitutive expression of the Pim-1 kinase prolongs survival of cytokine-deprived FDCP1 cells, partly via maintenance of Bcl-2 expression. Here, we show that Pim-1 colocalizes and physically interacts with the pro-apoptotic Bad protein and phosphorylates it in vitro on serine 112, which is a gatekeeper site for its inactivation. Furthermore, wild-type Pim-1, but not a kinase-deficient mutant, enhances phosphorylation of this site in FDCP1 cells and protects cells from the pro-apoptotic effects of Bad. Our results suggest that phosphorylation of Bad by Pim-1 is one of several mechanisms via which the Pim-1 kinase can enhance Bcl-2 activity and promote cell survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • COS Cells
  • Carrier Proteins / antagonists & inhibitors*
  • Carrier Proteins / metabolism
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Chlorocebus aethiops
  • Glutathione Transferase / genetics
  • Glutathione Transferase / metabolism
  • Interleukin-3 / pharmacology
  • Kinetics
  • Phosphorylation
  • Phosphoserine / metabolism*
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-pim-1
  • Recombinant Fusion Proteins / metabolism
  • Transfection
  • bcl-Associated Death Protein

Substances

  • Carrier Proteins
  • Interleukin-3
  • Proto-Oncogene Proteins
  • Recombinant Fusion Proteins
  • bcl-Associated Death Protein
  • Phosphoserine
  • Glutathione Transferase
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-pim-1