Mad2 is required for optimal hematopoiesis: Mad2 associates with c-Kit in MO7e cells

Shigeki Ito, Charlie R. Mantel, Myung Kwan Han, Sunanda Basu, Seiji Fukuda, Scott Cooper, Hal Broxmeyer

Research output: Contribution to journalArticle

10 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1923-1930
Number of pages8
JournalBlood
Volume109
Issue number5
DOIs
StatePublished - Mar 1 2007

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Stem Cell Factor
Hematopoiesis
Granulocyte-Macrophage Colony-Stimulating Factor
Bone
Bone Marrow
Granulocyte-Macrophage Progenitor Cells
Hematopoietic Stem Cells
Association reactions
M Phase Cell Cycle Checkpoints
Chromosome Segregation
Phosphorylation
Confocal microscopy
Macrophages
Annexin A5
Chromosomes
Immunoprecipitation
Confocal Microscopy
Assays
Cytoplasm
Phosphotransferases

ASJC Scopus subject areas

  • Hematology

Cite this

Ito, S., Mantel, C. R., Han, M. K., Basu, S., Fukuda, S., Cooper, S., & Broxmeyer, H. (2007). Mad2 is required for optimal hematopoiesis: Mad2 associates with c-Kit in MO7e cells. Blood, 109(5), 1923-1930. https://doi.org/10.1182/blood-2006-06-030841

Mad2 is required for optimal hematopoiesis : Mad2 associates with c-Kit in MO7e cells. / Ito, Shigeki; Mantel, Charlie R.; Han, Myung Kwan; Basu, Sunanda; Fukuda, Seiji; Cooper, Scott; Broxmeyer, Hal.

In: Blood, Vol. 109, No. 5, 01.03.2007, p. 1923-1930.

Research output: Contribution to journalArticle

Ito, S, Mantel, CR, Han, MK, Basu, S, Fukuda, S, Cooper, S & Broxmeyer, H 2007, 'Mad2 is required for optimal hematopoiesis: Mad2 associates with c-Kit in MO7e cells', Blood, vol. 109, no. 5, pp. 1923-1930. https://doi.org/10.1182/blood-2006-06-030841
Ito S, Mantel CR, Han MK, Basu S, Fukuda S, Cooper S et al. Mad2 is required for optimal hematopoiesis: Mad2 associates with c-Kit in MO7e cells. Blood. 2007 Mar 1;109(5):1923-1930. https://doi.org/10.1182/blood-2006-06-030841
Ito, Shigeki ; Mantel, Charlie R. ; Han, Myung Kwan ; Basu, Sunanda ; Fukuda, Seiji ; Cooper, Scott ; Broxmeyer, Hal. / Mad2 is required for optimal hematopoiesis : Mad2 associates with c-Kit in MO7e cells. In: Blood. 2007 ; Vol. 109, No. 5. pp. 1923-1930.
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