The PIM-2 Kinase Phosphorylates BAD on Serine 112 and Reverses BAD-induced Cell Death

Bin Yan, Marina Zemskova, Sheldon Holder, Vernon Chin, Andrew Kraft, Paivi J. Koskinen, Michael Lilly

Research output: Contribution to journalArticle

199 Scopus citations

Abstract

Hematopoietic growth factors mediate the survival and proliferation of blood-forming cells, but the mechanisms through which these proteins produce their effects are incompletely known. Recent studies have identified the pim family of kinases as mediators of cytokine-dependent survival signals. Several studies have identified substrates for the pim-1 kinase, but little is known about the other family members, pim-2 and pim-3. We have investigated potential functions for the pim-2 kinase in factor-dependent murine hematopoietic cells. We find that pim-2 mRNA and protein expression are regulated by cytokines similarly to pim-1. Three PIM-2 protein isoforms are produced in cytokine-treated cells. All three forms are active kinases, and the short (PIM-2(34 kDa)) form is the most active at enhancing survival of FDCP1 cells after cytokine withdrawal. This pro-survival function involves inhibition of apoptosis and caspase activation. Enforced expression of PIM-2(34 kDa) kinase does not appear to regulate expression of BCL-2, BCL-xL, BIM, or BAX proteins. However, the kinase can phosphorylate the pro-apoptotic protein BAD on serine 112, which accounts in part for its ability to reverse Bad-induced cell death. Our results indicate that pim-2 functions similarly topim-1 as a pro-survival kinase and suggest that BAD is a legitimate PIM-2 substrate.

Original languageEnglish (US)
Pages (from-to)45358-45367
Number of pages10
JournalJournal of Biological Chemistry
Volume278
Issue number46
DOIs
StatePublished - Nov 14 2003
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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