Calmodulin-dependent protein kinase IV regulates hematopoietic stem cell maintenance

Christine M. Kitsos, Uma Sankar, Maddalena Illario, Josep M. Colomer-Font, Andrew W. Duncan, Thomas J. Ribar, Tannishtha Reya, Anthony R. Means

Research output: Contribution to journalArticle

49 Scopus citations

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+ Scal+ 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.

Original languageEnglish (US)
Pages (from-to)33101-33108
Number of pages8
JournalJournal of Biological Chemistry
Volume280
Issue number39
DOIs
StatePublished - Sep 30 2005

    Fingerprint

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Kitsos, C. M., Sankar, U., Illario, M., Colomer-Font, J. M., Duncan, A. W., Ribar, T. J., Reya, T., & Means, A. R. (2005). Calmodulin-dependent protein kinase IV regulates hematopoietic stem cell maintenance. Journal of Biological Chemistry, 280(39), 33101-33108. https://doi.org/10.1074/jbc.M505208200