Impaired interleukin-3 response in Pim-1-deficient bone marrow-derived mast cells.
The mouse Pim-1 gene encodes two cytoplasmic serine-threonine-specific protein kinases. The gene has been found to be activated (overexpressed) by retroviral insertion in hematopoietic tumors in mice. Transgenic mice that overexpress Pim-1 (E mu-Pim-1) have a low incidence of spontaneous T-cell lymphomas and an increased susceptibility to Moloney murine leukemia virus and N-ethyl-N-nitrosourea-induced lymphomas. Apart from a slight enlargement of the spleen, no abnormalities were found in prelymphomatous transgenic mice. Inactivation of the Pim-1 gene in the germline of mice resulted in mice with a surprisingly subtle phenotype. Therefore, we investigated whether subtle effects of the absence of Pim-1 could be made visible during in vitro culturing of hematopoietic cells. We found that bone marrow-derived mast cells (BMMC) lacking Pim-1 had a distinct growth disadvantage when grown on interleukin (IL)-3, but not when stimulated by the factors IL-4, IL-9, or Steel factor (SF). This indicates a role for Pim-1 as a modulator of the IL-3 signal transduction pathway.
Domen
J
J
Division of Molecular Genetics, The Netherlands Cancer Institute, Amsterdam.
van der Lugt
N M
NM
Laird
P W
PW
Saris
C J
CJ
Clarke
A R
AR
Hooper
M L
ML
Berns
A
A
D000818:Animals; D001854:Bone Marrow Cells; D002454:Cell Differentiation; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology; D007377:Interleukin-3 / Q000502:physiology*; D008221:Lymphoid Tissue / Q000166:cytology; D008407:Mast Cells / Q000737:chemistry*; D051379:Mice; D008817:Mice, Mutant Strains; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000172:deficiency*; D051573:Proto-Oncogene Proteins c-pim-1; D019089:Stem Cell Factor
D016298:Hematopoietic Cell Growth Factors; D007377:Interleukin-3; D011518:Proto-Oncogene Proteins; D019089:Stem Cell Factor; C496636:Pim1 protein, mouse; D017346:Protein Serine-Threonine Kinases; D051573:Proto-Oncogene Proteins c-pim-1