Disease relevance of PCSK1

• In mouse models with established subcutaneous prostate (PC3) and orthotopic breast tumors (MDA-MB321), this combination treatment induced 80 to 85% inhibition of tumor growth without overt toxicity [1].
• A number of compounds in both the VS and the KOD series exhibited growth inhibitory effects against the human prostate cancer cell line PC3 at submicromolar concentrations [2].
• Thus, GAP-releasing enzyme (and other non-related proteins) were tested for their immunological reactivity with antisera raised against pituitary pro-hormone convertase 1/3 (PC1/3) and insulinoma PC2 [3].

High impact information on PCSK1

• The neutral activity was significantly immunodepleted by antiserum raised against bovine PC2/PC3, and together with specificity studies, suggests that the enzyme is a PC2-like serine protease [4].
• It is likely that these sequences represent the mature form of PC2 and PC3 in chromaffin granules [5].
• NH2-terminal sequence analysis of GpH gave two sequences which were aligned with residues 110-121 of PC2 and PC3 [5].
• Prohormone convertases PC1 and PC2 are enzymes involved in the intracellular processing of pro-neurotensin/neuromedin N (pro-NT/NN) through the regulated secretory pathway [6].
• In this study, we present evidence of the differential gene expression of pro-NT/NN, pro-PC1 and pro-PC2 in two cell lines established from the neuroendocrine ocular ciliary epithelium [6].

Chemical compound and disease context of PCSK1

• Effects of the antiandrogen flutamide on the expression of protein kinase C isoenzymes in LNCaP and PC3 human prostate cancer cells [7].

Biological context of PCSK1

• Differential regulation of gene expression of neurotensin and prohormone convertases PC1 and PC2 in the bovine ocular ciliary epithelium: possible implications on neurotensin processing [6].
• Molecular cloning from bovine adrenal medulla resulted in the isolation of cDNAs for bovine PC1 and PC2 with highly conserved primary sequences with respect to signal sequence, prosegment, catalytic domain, and P domain [8].

Anatomical context of PCSK1

• The cloned cDNAs detected expression of PC1 and PC2 mRNAs in bovine adrenal medulla [8].
• Different degrees of processing of secretogranin II in large dense core vesicles of bovine adrenal medulla and sympathetic axons correlate with their content of soluble PC1 and PC2 [9].

Associations of PCSK1 with chemical compounds

• Bovine PC1 and PC2 contained the catalytic triad residues Asp, His, Ser, which are identical to the triads in PC1 and PC2 from other mammalian species [8].
• Stimulation of bovine adrenal medulla by carbamoylcholine chloride induced the secretion of PC1 and PC2 [10].
• The chromaffin granule proenkephalin processing proteases have been characterized as the novel cysteine protease prohormone thiol protease (PTP), a 70-kDa aspartic proteinase, and the subtilisin-like PC1/3 and PC2 enzymes [11].
• No differences were found for dopamine beta-hydroxylase, prohormone convertase PC1, carboxypeptidase H and synaptophysin [12].
• In PC3 cells flutamide potentiated the expression of the four PKC isoenzymes in almost all conditions tested (FBS- and CSS-cultured cells) [7].

Analytical, diagnostic and therapeutic context of PCSK1

• It was concluded that the spot identified as GpH by two-dimensional gel electrophoresis contains the bovine counterparts of both PC2 and PC3 [5].
• The subcellular distribution of PC1, PC2 and furin was determined in bovine adrenal medulla by immunoblotting of fractions obtained by density gradient centrifugation [10].
• On the basis of indirect enzyme-linked immunosorbent (ELISA) and Western blot assays, GAP-releasing enzyme is now shown to be immunologically related to PC1/3 [3].

References