Submitted April 4, 2007
Accepted November 18, 2007
Pim-1 and Pim-2 kinases are required for efficient pre-B cell transformation by v-Abl oncogene
Ji-Long Chen, Andre Limnander, and Paul B. Rothman*
Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA, United States
* Corresponding author; email: paul-rothman{at}uiowa.edu.
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 can not 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 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.
