PgmNr D1038: Activation of Sona requires furin cleavage and autocatalysis.

Authors:
S.-S. Lee; J.-H. Won; G.-W. Kim; K.-O. Cho


Institutes
KAIST, DAEJEON, KR.


Keyword: wingless

Abstract:

ADAMTS (a disintegrin and metalloproteases with thrombospondin motif) family consists of secreted proteases, and is shown to cleave extracellular matrix proteins. Their malfunctions result in cancers and disorders in connective tissues. We have previously reported that a Drosophila ADAMTS named Sol narae (Sona) promotes Wnt/Wingless (Wg) signaling by modifying the activity and diffusion of Wg. Thus, spatiotemporal regulation of Wg signaling may be linked to the regulation of Sona activity. To become an active Sona, the prodomain of Sona has to be cleaved by furin, a proprotein convertase. To understand which processes are important for Sona activation, we generated mutations in five putative furin cleavage sites, three N-glycosylation sites, and carboxyl terminal region, and then examined which mutations affect the activation of Sona. We found that one of the five furin sites is essential for the activation of Sona, and N-glycosylation sites are not important for activation of Sona but for targeting Sona to the destined place. Interestingly, Sona has an autocatalytic site in the prodomain whose cleavage is prerequisite to the cleavage at the furin cleavage site. In addition, the carboxyl terminal region was also important for Sona processing. Taken together, the generation of active Sona requires sequential processing at the autocatalytic site and the furin site.