Mice deficient for all PIM kinases display reduced body size and impaired responses to hematopoietic growth factors.
The Pim family of proto-oncogenes encodes a distinct class of serine/threonine kinases consisting of PIM1, PIM2, and PIM3. Although the Pim genes are evolutionarily highly conserved, the contribution of PIM proteins to mammalian development is unclear. PIM1-deficient mice were previously described but showed only minor phenotypic aberrations. To assess the role of PIM proteins in mammalian physiology, compound Pim knockout mice were generated. Mice lacking expression of Pim1, Pim2, and Pim3 are viable and fertile. However, PIM-deficient mice show a profound reduction in body size at birth and throughout postnatal life. In addition, the in vitro response of distinct hematopoietic cell populations to growth factors is severely impaired. In particular, PIM proteins are required for the efficient proliferation of peripheral T lymphocytes mediated by synergistic T-cell receptor and interleukin-2 signaling. These results indicate that members of the PIM family of proteins are important but dispensable factors for growth factor signaling.
Mikkers
Harald
H
Division of Molecular Genetics and Centre of Biomedical Genetics, Netherlands Cancer Institute, Amsterdam, The Netherlands.
Nawijn
Martijn
M
Allen
John
J
Brouwers
Conny
C
Verhoeven
Els
E
Jonkers
Jos
J
Berns
Anton
A
D000818:Animals; D001824:Body Constitution; D002454:Cell Differentiation / Q000235:genetics; D002455:Cell Division; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D006410:Hematopoiesis / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D007376:Interleukin-2; D051379:Mice; D018345:Mice, Knockout; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051573:Proto-Oncogene Proteins c-pim-1; D011948:Receptors, Antigen, T-Cell; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology
D003115:Colony-Stimulating Factors; D007376:Interleukin-2; C094167:Pim2 protein, mouse; D011518:Proto-Oncogene Proteins; D011948:Receptors, Antigen, T-Cell; C496636:Pim1 protein, mouse; C488192:Pim3 protein, mouse; D017346:Protein Serine-Threonine Kinases; D051573:Proto-Oncogene Proteins c-pim-1; C406031:proto-oncogene proteins pim