Calmodulin-dependent protein kinase IV regulates hematopoietic stem cell maintenance.

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Kitsos, CM; Sankar, U; Illario, M; Colomer-Font, JM; Duncan, AW; Ribar, TJ; Reya, T; Means, AR

Published Date

  • September 30, 2005

Published In

Volume / Issue

  • 280 / 39

Start / End Page

  • 33101 - 33108

PubMed ID

  • 16020540

International Standard Serial Number (ISSN)

  • 0021-9258

Digital Object Identifier (DOI)

  • 10.1074/jbc.M505208200

Language

  • eng

Conference Location

  • United States