Pim-1 levels determine the size of early B lymphoid compartments in bone marrow.
The mouse proto-oncogene Pim-1, which encodes two cytoplasmic serine-threonine-specific protein kinases, is frequently activated by proviral insertion in murine leukemia virus-induced hematopoietic tumors. Transgenic mice overexpressing Pim-1 show a low incidence of spontaneous T cell lymphomas, whereas null mutant mice lack an obvious phenotype. We have analyzed the early B lymphoid compartment from both null mutant and E mu-Pim-1 transgenic mice. The level of Pim-1 expression appears to be a determining factor in the ability of these cells to respond to the growth factors interleukin 7 (IL-7) and SF (steel factor). The impaired response in null mutant mice could be rescued by introduction of a functional Pim-1 transgene. Moreover, overexpression of Pim-1 facilitates the derivation of primitive lymphoid cell lines that are dependent on combined stimulation with IL-7 and SF or insulin-like growth factor 1. These results for the first time identify the involvement of Pim-1 in a normal cellular function, as an important regulator of early B lymphopoiesis in mice.
Domen
J
J
Division of Molecular Genetics, The Netherlands Cancer Institute, Amsterdam.
van der Lugt
N M
NM
Acton
D
D
Laird
P W
PW
Linders
K
K
Berns
A
A
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D001853:Bone Marrow / Q000378:metabolism*; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D015848:Interleukin-5 / Q000494:pharmacology; D015851:Interleukin-7 / Q000494:pharmacology; D007378:Interleukins / Q000494:pharmacology*; D007700:Kinetics; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000302:isolation & purification; D051573:Proto-Oncogene Proteins c-pim-1; D011519:Proto-Oncogenes; D011994:Recombinant Proteins / Q000494:pharmacology
D015848:Interleukin-5; D015851:Interleukin-7; D007378:Interleukins; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; D016173:Macrophage Colony-Stimulating Factor; D011505:Protein-Tyrosine Kinases; C496636:Pim1 protein, mouse; D017346:Protein Serine-Threonine Kinases; D051573:Proto-Oncogene Proteins c-pim-1