The Relevance of Protein Kinase C Activation, Glucose Transport and ATP Generation in the Response of Haemopoietic Cells to Growth Factors

Abstract

Haemopoietic cells differ from most other cell types in that their survival in vitro absolutely requires the presence of specific growth factors. For example, the proliferation and development of multipotent haemopoietic stem cells in vitro requires the presence of a growth factor called interleukin-3 (IL-3); in its absence, the cells die. Similarly, the committed progenitor cells which arise as a consequence of differentiation of the multipotent stem cells also require factors for their growth and development in vitro. These growth factors include IL-3 (which, in addition to acting on stem cells, also acts on the more mature differentiating cells) and a variety of lineage-restricted molecules such as granulocyte/macrophage colony-stimulating factor (GM-CSF) (Burgess and Nicola 1983; Gough et al. 1984; Metcalf 1985), erythropoietin (Eaves and Eaves 1984), macrophage colony-stimulating factor (M-CSF or CSF-1) (Stanley and Jubinsky 1984; Burgess and Nicola 1983; Metcalf 1985) to name just a few (see Gough, this Vol.). In the absence of these growth factors, the committed progenitor cells die (Metcalf 1977). In their presence, the primitive stem cells and progenitor cells undergo growth and differentiation to produce the mature functional end cells, erythrocytes, neutrophils, macrophages and so on (Metcalf 1977). It is also clear that the growth factors are required continuously throughout the developmental programme: removal of the growth factor at any stage during the development into the mature cells leads to a cessation of growth and to death of the developing clone.