A Mutation of Furin Causes the Lack of Precursor-Processing Activity in Human Colon Carcinoma LoVo Cells

Abstract

Furin has been proposed to be the endoprotease responsible for precursor cleavage at Arg-X-Lys/Arg-Arg (RXK/RR) sites within the constitutive secretory pathway. However, there was a possibility that other protease(s) is involved in this cleavage. We here characterized furin in human colon carcinoma LoVo cells, since these cells lacked the endogenous processing activity toward RXK/RR sites and recovered the activity by transfection of furin cDNA. Furin cDNA cloned from LoVo cells had one nucleotide deletion in the region covering the homo B domain which is essential for the endoproteolytic activity. LoVo cells transfected with a furin construct with the mutation showed no activity. Based on these data, we conclude that furin is the endoprotease that is involved in the precursor cleavage at RXK/RR sites within the constitutive secretory pathway.