The serine/threonine kinase Pim-2 is a transcriptionally regulated apoptotic inhibitor

  1. Casey J. Fox1,2,
  2. Peter S. Hammerman1,2,
  3. Ryan M. Cinalli1,2,
  4. Stephen R. Master1,3,
  5. Lewis A. Chodosh1,2,3, and
  6. Craig B. Thompson1,2,3,4
  1. 1 Abramson Family Cancer Research Institute, Philadelphia, Pennsylvania 19104, USA
  2. 2 Department of Cancer Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
  3. 3 Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA

Abstract

Growth factor withdrawal results in the termination of factor-dependent transcription. One transcript that declines rapidly following growth factor deprivation of hematopoietic cells is the serine/threonine kinase pim-2. When constitutively expressed, Pim-2 conferred long-term resistance to a variety of apoptotic stimuli including growth factor withdrawal and endogenous levels of Pim-2 contributed to growth factor-mediated apoptotic resistance. Pim-2 expression maintained cell size and mitochondrial potential independently of the PI3K/Akt/TOR pathway. Pim-2-dependent maintenance of cell size and survival correlated with its ability to maintain rapamycin-resistant phosphorylation of the translational repressor 4E-BP1 and phosphorylation of the BH3 protein BAD. These results establish Pim-2 as a direct link between growth factor-induced transcription and a novel, kinase-dependent pathway that promotes cell-autonomous survival.

Keywords

Footnotes

  • Corresponding author.

  • Article published online ahead of print. Article and publication date are at http://www.genesdev.org/cgi/doi/10.1101/gad.1105003.

  • 4 E-MAIL craig{at}mail.med.upenn.edu; FAX (215) 746-5511.

    • Accepted June 2, 2003.
    • Received April 17, 2003.
| Table of Contents

G&D Most Read

View all ...

Life Science Alliance