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Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
09:18

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

The PIM-2 kinase phosphorylates BAD on serine 112 and reverses BAD-induced cell death

Bin Yan1, Marina Zemskova, Sheldon Holder

  • 1Center for Molecular Biology & Gene Therapy, the Department of Microbiology, Loma Linda University School of Medicine, Loma Linda, California 92354, USA.

The Journal of Biological Chemistry
|September 5, 2003
PubMed

Insights

The pim-2 kinase, a mediator of cytokine signals, promotes hematopoietic cell survival by inhibiting apoptosis. It phosphorylates the pro-apoptotic protein BAD, partially reversing cell death.

Area of Science:

  • Hematology
  • Molecular Biology
  • Cell Signaling

Background:

  • Hematopoietic growth factors are crucial for blood cell survival and proliferation, but their precise mechanisms are not fully understood.
  • The pim kinase family, including pim-1, pim-2, and pim-3, are known mediators of cytokine-dependent survival signals.
  • While pim-1 substrates are identified, the functions of pim-2 and pim-3 remain largely unexplored.

Purpose of the Study:

  • To investigate the role of pim-2 kinase in factor-dependent murine hematopoietic cells.
  • To elucidate the pro-survival mechanisms mediated by pim-2 in response to cytokine signaling.

Main Methods:

  • Analysis of pim-2 mRNA and protein expression in response to cytokines.
  • Identification and characterization of PIM-2 protein isoforms.
  • Assessment of PIM-2 kinase activity and its effect on cell survival and apoptosis.
  • Investigation of PIM-2's interaction with apoptosis-related proteins, including BAD.

Main Results:

  • Pim-2 expression is regulated by cytokines, similar to pim-1.
  • Three active PIM-2 protein isoforms are produced, with the short form (PIM-2(34 kDa)) being most effective in enhancing survival.
  • PIM-2(34 kDa) inhibits apoptosis and caspase activation, but does not significantly alter BCL-2 family protein expression.
  • PIM-2 phosphorylates the pro-apoptotic protein BAD on serine 112, contributing to its pro-survival function.

Conclusions:

  • Pim-2 functions as a pro-survival kinase in hematopoietic cells, analogous to pim-1.
  • Phosphorylation of BAD on serine 112 is a key mechanism by which PIM-2 promotes cell survival.
  • BAD is identified as a functional substrate of PIM-2 kinase.

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