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

198 Citations (Scopus)

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

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Cell death
Serine
Cell Death
Phosphotransferases
Cytokines
Proto-Oncogene Proteins c-pim-1
Apoptosis Regulatory Proteins
Proteins
Aptitude
Caspases
Blood Cells
Cell Survival
Intercellular Signaling Peptides and Proteins
Protein Isoforms
Substrates
Apoptosis
Messenger RNA
Blood
Chemical activation
Cells

ASJC Scopus subject areas

  • Biochemistry

Cite this

The PIM-2 Kinase Phosphorylates BAD on Serine 112 and Reverses BAD-induced Cell Death. / Yan, Bin; Zemskova, Marina; Holder, Sheldon; Chin, Vernon; Kraft, Andrew; Koskinen, Paivi J.; Lilly, Michael.

In: Journal of Biological Chemistry, Vol. 278, No. 46, 14.11.2003, p. 45358-45367.

Research output: Contribution to journalArticle

Yan, B, Zemskova, M, Holder, S, Chin, V, Kraft, A, Koskinen, PJ & Lilly, M 2003, 'The PIM-2 Kinase Phosphorylates BAD on Serine 112 and Reverses BAD-induced Cell Death', Journal of Biological Chemistry, vol. 278, no. 46, pp. 45358-45367. https://doi.org/10.1074/jbc.M307933200
Yan, Bin ; Zemskova, Marina ; Holder, Sheldon ; Chin, Vernon ; Kraft, Andrew ; Koskinen, Paivi J. ; Lilly, Michael. / The PIM-2 Kinase Phosphorylates BAD on Serine 112 and Reverses BAD-induced Cell Death. In: Journal of Biological Chemistry. 2003 ; Vol. 278, No. 46. pp. 45358-45367.
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