Extracellular Signal-Regulated Kinases and G Protein-Coupled Receptors in Megakaryocytic Human Erythroleukemia Cells: Selective Activation, Differential Regulation, and Dissociation

Extracellular signal-regulated kinases 1 and 2 (ERK1/2) are a group of kinases that play an important role in proliferation and differentiation. In megakaryocyte-like human erythroleukemia (HEL) cells, ERK2 was found to be predominantly expressed and strongly activated by prostaglandin (PG) E2, thrombin, and epinephrine. On the other hand, adenosine, ADP, ATP, and UTP did not significantly increase ERK1/2 phosphorylation. How-ever, of the agonists tested, only ADP was able to stimulate thymidine uptake. Pretreatment with pertussis toxin abolished the PGE2 response but had less of an effect on thrombin. PGE2- and thrombin-induced ERK1/2 activation was mimicked by 4--phorbol-12-myristate-13-acetate and ionomycin and blocked by mitogen-activated protein kinase kinase inhibitor 1,4 diamino-2,3-dicyano-1,4-bis[2-aminophenylthio]buta