Impaired Interleukin-3 Response in Pim-1-Deficient Bone Marrow-Derived Mast Cells

• Published in: Blood Vol. 82; no. 5; pp. 1445 - 1452
• Main Authors: Domen, Jos, van der Lugt, Nathalie M.T., Laird, Peter W., Saris, Chris J.M., Clarke, Alan R., Hooper, Martin L., Berns, Anton
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 01.09.1993; The Americain Society of Hematology
• Subjects: Animals; Biological and medical sciences; Bone Marrow Cells; Cell Differentiation; Cell differentiation, maturation, development, hematopoiesis; Cell Division - drug effects; Cell physiology; Cells, Cultured; Fundamental and applied biological sciences. Psychology; Hematopoietic Cell Growth Factors - pharmacology; Interleukin-3 - physiology; Lymphoid Tissue - cytology; Mast Cells - chemistry; Mice; Mice, Mutant Strains; Molecular and cellular biology; Protein-Serine-Threonine Kinases; Proto-Oncogene Proteins - deficiency; Proto-Oncogene Proteins c-pim-1; Stem Cell Factor; Cell culture; Hematopoiesis; Interleukin 3; Cytokine; Hematopoietic cell; Bone marrow; Mast cell
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V82.5.1445.1445

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 (Eμ-Pim-1) have a low incidence of spontaneous T-cell lymphomas and an increased susceptibility to Moloney murine leukemia virus and N-ethyl-N-ni-trosourea-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.