The propeptide of preprosomatostatin mediates intracellular transport and secretion of alpha-globin from mammalian cells

Approximately 50% of processed mature globin was stored intracellularly with a half-life >6 h. It was therefore of interest to determine if globin was targeted to the regulated secretory pathway (Fig. 8) . Cells were pulse labeled for 15 min and chased for 2 h, the medium was then changed and the cells incubated for an additional 2 h in the absence (Fig. 8, lanes 4 and 8) or presence of the secretagogue, 8-Br-cAMP (Fig. 8, lanes 5 and 9) . During the 120-min chase in the absence of 8-Br-cAMP, unprocessed PRO-GLO and mature globin were secreted (Fig. 8, lane 6 ) but a significant level of both molecules was still present intracellularly at 240 min of chase (Fig. 8, lanes 3 and 4) . However, in the presence of 8-Br-cAMP (cf. Fig. 8, lanes 5 and 9) , 90 % of both mature globin and PRO-GLO were secreted and virtually no globin-related material remained intracellular (Fig. 8, lane 5) . We conclude that the release of stored globin and PRO-GLO in response to 8-Br-cAMP indicated targeting to the regulated pathway.