Signal transduction events in in vitro megakaryocytopoiesis

Understanding of the events following factor-mediated megakaryocyte development is hindered by a lack of adequate quantities of purified progenitor cells or progenitor cell lines. In order to study the intracellular processes activated during development, probes of various signal transduction systems are used to perturb megakaryocyte colony formation. Studies utilizing tumor promoting phorbol diesters and calcium ionophores show that protein kinase C and calcium mobilization (and/or influx) are activated during megakaryocyte development. Examination of the adenylate cyclase complex, with agonists such as cholera toxin etc., implicate cyclic AMP as another mediator of growth-factor responsiveness. Finally, synergistic interactions occur between the calcium-protein kinase C system and the adenylate cyclase complex. These observations corroborate the multifactorial regulation of megakaryocytopoiesis postulated by Williams and coworkers. The data further provide an intracellular mechanism(s) by which megakaryocytic growth factors regulate cellular development.