DISSOCIATION OF THE COMPLEX BETWEEN THE NEUROENDOCRINE CHAPERONE 7B2 AND PROHORMONE CONVERTASE PC2 IS NOT ASSOCIATED WITH PROPC2 MATURATION

7B2 is a highly conserved neuroendocrine protein that is associated wi th the preform of the prohormone convertase PC2 in the early stages of the secretory pathway in intermediate pituitary cells of Xenopus laev is. Subsequent processing of 7B2 and dissociation of the 7B2/proPC2 co mplex is thought to be associated with the conversion of proPC2 to the mature enzyme. Here, we report that, in both Xenopus and mouse interm ediate pituitary cells, proPC2 maturation does not take place when the proenzyme is associated with the 7B2 precursor and that, in contrast to the previous notion, dissociation of the complex between proPC2 and the N-terminal 7B2 fragment precedes, and is thus not directly linked to, proPC2 maturation. In vitro, conversion of newly synthesized proP C2 was efficiently blocked by recombinant 7B2, and studies with trunca tion mutants indicated that a short segment in the C-terminal region o f 7B2 is necessary and sufficient for this inhibitory effect. Our resu lts indicate that, after 7B2 precursor processing and dissociation of the N-terminal fragment, the C-terminal fragment of 7B2, may remain as sociated with proPC2, thereby preventing autocatalytic conversion of t he proenzyme until the appropriate site for activation in the secretor y pathway is reached.