In Vitro studies on the regulation of erythropoiesis by erythropoietin and stem cell factor

In this thesis we set out to unravel the components of the EpoR/c-Kit signalling complex to gain insight into the intracellular proteins involved in Epo and SCF regulated differentiation, survival and expansion. At present the proteins responsible for these processes are poorly described though recent data indicates that PI3K dependent signal transduction drives the expansion of erythroid progenitors. Absence of these signals results in accelerated differentiation. The signal transducing mediators downstream of PI3K may thus be part of an important switch, responsible for the regulation of the amounts of erythrocytes produced. Due to their described role in signal amplification and mitogenic signalling we focussed on PI3K regulated Tee-family kinases and docking molecules activated by SCF and/or Epo