Akt signaling regulates side population cell phenotype via Bcrp1 translocation.
Publication/Presentation Date
10-3-2003
Abstract
Akt is an important regulator of cell survival, growth, and glucose metabolism in many cell types, but the role of this signaling molecule in hematopoietic stem cells is poorly defined. Side population (SP) cells are enriched for hematopoietic stem cell activity and are defined by their ability to efficiently efflux Hoechst 33342. Bone marrow from Akt1-null mice exhibited a reduced SP fraction. However, bone marrow cellularity, growth factor-responsive progenitor cultures, and engraftable stem cells were normal in these mice. Treatment of bone marrow with LY294002, an inhibitor of the Akt effector protein phosphatidylinositol 3-kinase, led to a reversible loss of the SP fraction. Bcrp1, which encodes the Hoechst dye transporter, was translocated from the membrane to the intracellular compartment under conditions that promote the SP-depleted state. Lentivirus-mediated overexpression of Akt1 in bone marrow markedly increased the SP fraction, whereas there was no effect on bone marrow from Bcrp(-/-) mice. These data suggest that Akt signaling modulates the SP cell phenotype by regulating the expression of Bcrp1.
Volume
278
Issue
40
First Page
39068
Last Page
39075
ISSN
0021-9258
Published In/Presented At
Mogi, M., Yang, J., Lambert, J. F., Colvin, G. A., Shiojima, I., Skurk, C., Summer, R., Fine, A., Quesenberry, P. J., & Walsh, K. (2003). Akt signaling regulates side population cell phenotype via Bcrp1 translocation. The Journal of biological chemistry, 278(40), 39068–39075. https://doi.org/10.1074/jbc.M306362200
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
12851395
Department(s)
Administration and Leadership
Document Type
Article