Identification of a cDNA encoding a second putative prohormone convertase related to PC2 in AtT20 cells and islets of Langerhans.

Abstract

PC2 and furin are two recently identified members of a class of mammalian proteins homologous to the yeast precursor processing protease kex2 and the bacterial subtilisins. We have used the polymerase chain reaction to identify and clone a cDNA (PC3) from the mouse AtT20 anterior pituitary cell line that represents an additional member of this growing family of mammalian proteases. PC3 encodes a 753-residue protein that begins with a signal peptide and contains a 292-residue domain closely related to the catalytic modules of PC2, furin, and kex2. Within this region 58%, 65%, and 50% of the amino acids of PC3 are identical to those of the aligned PC2, furin, and kex2 sequences, respectively, and the catalytically important Asp, His, and Ser residues are all conserved. On Northern blots, PC3 hybridizes to two transcripts of 3 and 5 kilobases. Tissue distribution studies indicate that both PC2 and PC3 are expressed in a variety of neuroendocrine tissues, including pancreatic islets and brain, but are not expressed in liver, kidney, skeletal muscle, and spleen. The high degree of similarity of PC3, PC2, and furin suggests that they are all members of a superfamily of mammalian proteases that are involved in the processing of prohormones and/or other protein precursors. In contrast to furin, PC3, like PC2, lacks a hydrophobic transmembrane anchor, but it has a potential C-terminal amphipathic helical segment similar to the putative membrane anchor of carboxypeptidase H. These and other differences suggest that these proteins carry out compartmentalized proteolysis within cells, such as processing within regulated versus constitutive secretory pathways.

Molluscan putative prohormore convertases: Structural diversity in the central nervous system of Lymnaea stagnalis

“…Recently, the coding sequences for a number of vertebrate processing enzymes were reported, i.e. furin [3][4][5], PCI/PC3 [6][7][8][9], PC2 [7,10,11], and PC4 [12]. Furin has been shown to correctly process several precursor proteins, e.g.…”

Prohormone Convertase 1 Is Necessary for the Formation of Cholecystokinin 8 in Rin5F and STC-1 Cells

“…The cloning of prohormone convertase 1 (PC1) (14,15), also known as PC3, a member of the subtilisin family of enzymes, has identified another candidate. PC1 is a Ca 2ϩ -dependent serine endoprotease known to cleave propeptides at dibasic residues (16,17), and there is increasing evidence that it can also cleave at mono-arginyl sites as well (18,19).…”

Distinct mRNA expression of the highly homologous convertases PC5 and PACE4 in the rat brain and pituitary

“…The discovery of kexin, an endoprotease that performs such functions in May 23, 1994: revised Aug. 24, 1994accepted Sept. 6, 1994 yeast, lead to the identification of its mammalian homologs (Seidah, 1991). So far, six subtilisin/kexin-like mammalian prohormone convertases have been characterized and named furin (Roebroek et al, 1986;Van de Ven et al, 1990;or PACE, Barr et al, 1991) PC1 (Seidah et al, 1990(Seidah et al, , 1991b; also named PC3, Smeekens et al, 1991), PC2 (Seidah et al, 1990;Smeekens arid Steiner, 1990), PC4 (Nakayama et al, 1992; PACE4 (Kiefer et al, 1991), and PC5 (Lusson et al, 1993; also named PC6, Nakagawa et al, 1993a). Previous studies showed the ubiquitous distribution of furin mRNA in the CNS encompassing both neuronal and glial cells, whereas PC1 and PC2 mRNAs are restricted to neurons and endocrine cells (Seidah et al, 1990(Seidah et al, , 1991Day et al, 1992Day et al, , 1993Schafer et al, 1993).…”