Mad2 is Required for Optimal Hematopoiesis: Mad2 Associates with C-kit in Mo7e Cells.
From: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis 46202, USA.
Blood
- Publish Date: Mar 2007
- ISSN: 0006-4971
- Volume: 109
- Issue: 5
- Pages: 1923-30
- Medium: Print
- Language: English
- Citation (JAMA): Ito Shigeki, Mantel Charlie R, Han Myung-Kwan, et al. Mad2 is Required for Optimal Hematopoiesis: Mad2 Associates with C-kit in Mo7e Cells.. Blood Mar 2007;109:1923-30
Abstract
Mitotic arrest deficiency 2 (Mad2) is a component of mitotic spindle checkpoint proteins and is essential for accurate chromosome segregation. We investigated a role for Mad2 in hematopoiesis using Mad2-haploinsufficient (Mad2+/-) mice. Mad2+/- bone marrow (BM) and spleen manifested decreased absolute numbers and cycling status of immature, but not mature, hematopoietic progenitor cells. Mad2+/- BM granulocyte-macrophage colony-forming units (CFU-GMs) did not manifest synergistic proliferation in response to stem cell factor (SCF) plus GM-CSF. The percentage of annexin V+ cells was higher in Mad2+/- than Mad2+/+c-Kit+lin- BM after culture with SCF and GM-CSF. However, no significant difference in phosphorylation of extracellular signal-related kinase (Erk1/2) at Thr202/Tyr204 and Akt at Ser473 between Mad2+/- and Mad2+/+BM c-Kit+lin- cells was observed. Immunoprecipitation assays performed in human MO7e cells demonstrated physical association of c-Kit with Mad2. Moreover, stimulation with SCF plus GM-CSF led to dissociation of Mad2 from c-Kit. Confocal microscopy demonstrated that Mad2 colocalized with c-Kit in the cytoplasm of MO7e cells. These results suggest that Mad2 is involved in synergistic growth of immature hematopoietic progenitor cells in response to SCF plus GM-CSF, effects that may be mediated via physical association of Mad2 with c-Kit.
Mesh Headings (Keywords): Animals, Apoptosis, Bone Marrow Cells, Cell Cycle Proteins, Cell Line, Cytokines, Cytoplasm, Granulocyte-Macrophage Colony-Stimulating Factor, Haplotypes, Hematopoiesis, Humans, Mice, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinase 3, Protein Binding, Proto-Oncogene Proteins c-akt, Proto-Oncogene Proteins c-kit, Spleen, Stem Cell Factor
Check for Full Text / PubMed Unique Identifier (PMID): 17038523
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