Pim-1 and Pim-2 kinases are required for efficient pre-B-cell transformation by v-Abl oncogene

Ji Long Chen, Andre Limnander, Paul B Rothman

Research output: Contribution to journalArticle

Abstract

The precise mechanisms by which Abl oncogenes transform hematopoietic cells are unknown. We have examined the role of Pim kinases in v-Abl-mediated transformation. In v-Abl transformants, expression of Pim-1 and Pim-2, but not Pim-3, is dependent on Abl kinase activity. Transformation assays demonstrate that v-Abl cannot efficiently transform bone marrow cells derived from Pim-1-/-/Pim-2-/- mice. Ectopic expression of either Pim-1 or Pim-2 in Pim-1-/-/Pim-2-/- cells restores transformation by v-Abl, strongly suggesting that either Pim-1 or Pim-2 is required for v-Abl-mediated tumorigenesis. Interestingly, the combined deficiency of Pim-1, Pim-2, and Suppressor of Cytokine Signalling (SOCS)-1 resulted in partial restoration of v-Abl transformation efficiency. In addition, Pim kinases are involved in modification of SOCS-1 and in regulating SOCS-1 protein levels in v-Abl - transformed cells. Furthermore, Pim kinases regulate the proapoptotic proteins Bcl-XS and BAD. Pim kinases inhibit the expression of Bcl-XS. Pim deficiency decreases the phosphorylation levels of BAD, whereas ectopic expression of Pim-1 increases the amount of phospho-BAD. This correlates with an increased protection from apoptosis in Abl transformants expressing Pim kinases. Together, these data suggest that Pim kinases play a key role in the v-Abl transformation, possibly via participating in modulation of SOCS-1 and via regulating the apoptotic signaling.

Original languageEnglish (US)
Pages (from-to)1677-1685
Number of pages9
JournalBlood
Volume111
Issue number3
DOIs
StatePublished - 2008
Externally publishedYes

Fingerprint

Proto-Oncogene Proteins c-pim-1
abl Genes
B-Lymphoid Precursor Cells
Phosphotransferases
Cells
Cytokines
bcl-X Protein
Phosphorylation
Bone Marrow Cells
Restoration
proto-oncogene proteins pim
Assays
Bone
Carcinogenesis
Modulation
Apoptosis

ASJC Scopus subject areas

  • Hematology

Cite this

Pim-1 and Pim-2 kinases are required for efficient pre-B-cell transformation by v-Abl oncogene. / Chen, Ji Long; Limnander, Andre; Rothman, Paul B.

In: Blood, Vol. 111, No. 3, 2008, p. 1677-1685.

Research output: Contribution to journalArticle

Chen, Ji Long ; Limnander, Andre ; Rothman, Paul B. / Pim-1 and Pim-2 kinases are required for efficient pre-B-cell transformation by v-Abl oncogene. In: Blood. 2008 ; Vol. 111, No. 3. pp. 1677-1685.
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abstract = "The precise mechanisms by which Abl oncogenes transform hematopoietic cells are unknown. We have examined the role of Pim kinases in v-Abl-mediated transformation. In v-Abl transformants, expression of Pim-1 and Pim-2, but not Pim-3, is dependent on Abl kinase activity. Transformation assays demonstrate that v-Abl cannot efficiently transform bone marrow cells derived from Pim-1-/-/Pim-2-/- mice. Ectopic expression of either Pim-1 or Pim-2 in Pim-1-/-/Pim-2-/- cells restores transformation by v-Abl, strongly suggesting that either Pim-1 or Pim-2 is required for v-Abl-mediated tumorigenesis. Interestingly, the combined deficiency of Pim-1, Pim-2, and Suppressor of Cytokine Signalling (SOCS)-1 resulted in partial restoration of v-Abl transformation efficiency. In addition, Pim kinases are involved in modification of SOCS-1 and in regulating SOCS-1 protein levels in v-Abl - transformed cells. Furthermore, Pim kinases regulate the proapoptotic proteins Bcl-XS and BAD. Pim kinases inhibit the expression of Bcl-XS. Pim deficiency decreases the phosphorylation levels of BAD, whereas ectopic expression of Pim-1 increases the amount of phospho-BAD. This correlates with an increased protection from apoptosis in Abl transformants expressing Pim kinases. Together, these data suggest that Pim kinases play a key role in the v-Abl transformation, possibly via participating in modulation of SOCS-1 and via regulating the apoptotic signaling.",
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