Calmodulin-dependent Protein Kinase IV Regulates Hematopoietic Stem Cell Maintenance

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 fai...

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Bibliographic Details
Published in:The Journal of biological chemistry 2005-09, Vol.280 (39), p.33101-33108
Main Authors: Kitsos, Christine M., Sankar, Uma, Illario, Maddalena, Colomer-Font, Josep M., Duncan, Andrew W., Ribar, Thomas J., Reya, Tannishtha, Means, Anthony R.
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Calcium-Calmodulin-Dependent Protein Kinase Type 4
Calcium-Calmodulin-Dependent Protein Kinases - genetics
Calcium-Calmodulin-Dependent Protein Kinases - metabolism
Cell Proliferation
Cell Transplantation
Cells, Cultured
Gene Expression Regulation, Enzymologic
Hematopoietic Stem Cells - cytology
Hematopoietic Stem Cells - enzymology
Hematopoietic Stem Cells - physiology
Homeostasis
Mice
Mice, Congenic
Mice, Knockout
Models, Biological
Phosphorylation
Proto-Oncogene Proteins c-bcl-2 - metabolism
Serine - metabolism
Time Factors
Transplantation, Homologous
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Summary: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.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M505208200