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Calmodulin-dependent protein kinase IV regulates hematopoietic stem cell maintenance
- Source :
- The Journal of biological chemistry. 280(39)
- Publication Year :
- 2005
-
Abstract
- The hematopoietic stem cell (HSC) gives rise to all mature, terminally differentiated cells of the blood. Here we show that calmodulin-dependent protein kinase IV (CaMKIV) is present in c-Kit+ ScaI+ Lin(-/low) hematopoietic progenitor cells (KLS cells) and that its absence results in hematopoietic failure, characterized by a diminished KLS cell population and by an inability of these cells to reconstitute blood cells upon serial transplantation. KLS cell failure in the absence of CaMKIV is correlated with increased apoptosis and proliferation of these cells in vivo and in vitro. In turn, these cell biological defects are correlated with decreases in CREB-serine 133 phosphorylation as well as in CREB-binding protein (CBP) and Bcl-2 levels. Re-expression of CaMKIV in Camk4-/- KLS cells results in the rescue of the proliferation defects in vitro as well as in the restoration of CBP and Bcl-2 to wild type levels. These studies show that CaMKIV is a regulator of HSC homeostasis and suggest that its effects may be in part mediated via regulation of CBP and Bcl-2.
- Subjects :
- Time Factors
Cell Transplantation
Cellular differentiation
Cell
Population
Apoptosis
Biology
Biochemistry
Models, Biological
Gene Expression Regulation, Enzymologic
Mice
Mice, Congenic
medicine
Serine
Animals
Homeostasis
Transplantation, Homologous
Phosphorylation
education
Protein kinase A
Molecular Biology
Cells, Cultured
Cell Proliferation
Mice, Knockout
education.field_of_study
Hematopoietic stem cell
Cell Biology
Hematopoietic Stem Cells
Cell biology
Haematopoiesis
medicine.anatomical_structure
Proto-Oncogene Proteins c-bcl-2
Calcium-Calmodulin-Dependent Protein Kinases
Cancer research
Calcium-Calmodulin-Dependent Protein Kinase Type 4
Subjects
Details
- ISSN :
- 00219258
- Volume :
- 280
- Issue :
- 39
- Database :
- OpenAIRE
- Journal :
- The Journal of biological chemistry
- Accession number :
- edsair.doi.dedup.....220d8c77d3d8149153cc84f9280b92df