The role of the PI3K-PKB signaling module in regulation of hematopoiesis

Bone marrow homeostasis is controlled by a series of complex cell fate decisions that determine whether hematopoietic stem and progenitor cells divide, differentiate or die. Exquisite control of the stem cell niche is crucial for the correct maintenance of blood cell production, allowing inductive external signals to modulate stem cell self-renewal or increased production of specific blood cell lineages. Since the first bone marrow transplantation more than 40 years ago, research has been focused on understanding the molecular processes regulating hematopoietic stem cell function. While our appreciation of the transcriptional regulators of hematopoiesis has developed considerably, the role of specific intracellular signal transduction modules remains surprisingly undefined. One such module includes phosphatidylinostiol 3-kinase (PI3K) and protein kinase B (PKB/c-akt). The identification and cloning of PI3K and PKB in the early 1990s has resulted in the publication of a large body of literature providing e...