Regulation of CREB activation by p38 mitogen activated protein kinase during human primary erythroblast differentiation.

Among the molecular events underlying erythroid differentiation, we analyzed the signalling
pathway leading to cAMP response element binding (CREB) nuclear transcription factor activation.
Normal donor blood light density cells differentiated to pro-erythroblasts during the proliferative phase
(10 days) of the Human Erithroblast Massive Amplification (HEMA) culture, and to orthochromatic
erythroblasts, during the differentiative phase (4 additional days) of the culture. Since erythropoietin
was present all over the culture, also pro-erythroblasts left in proliferative medium for 14 days continued
their maturation without reaching the final steps of differentiation. p38 Mitogen Activated Protein
Kinase (p38 MAPK) and CREB maximal activation occurred upon 4 days of differentiation induction,
whereas a lower activation was detectable in the cells maintained in parallel in proliferative medium
(14 days). Interestingly, when SB203580, a specific p38 MAPK inhibitor, was added to the culture the
percentage of differentiated cells decreased along with p38 MAPK and CREB phosphorylation. All in
all, our results evidence a role for p38 MAPK in activating CREB metabolic pathway in the events
leading to erythroid differentiation.