A completed KLK activome profile: investigation of activation profiles of KLK9, 10, and 15

• Published in: Biological chemistry Vol. 390; no. 4; pp. 373 - 377
• Main Authors: Yoon, Hyesook, Blaber, Sachiko I., Debela, Mekdes, Goettig, Peter, Scarisbrick, Isobel A., Blaber, Michael
• Format: Journal Article
• Language: English
• Published: Germany Walter de Gruyter 01.04.2009
• Subjects: activation cascade; activome; Electrophoresis, Agar Gel; Gene Expression Profiling; Humans; kallikrein; kallikrein-related peptidases (KLKs); Kallikreins - genetics; Kallikreins - metabolism; protease; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - metabolism
• ISSN: 1431-6730; 1437-4315
• DOI: 10.1515/BC.2009.026

We previously reported the activation profiles of the human kallikrein-related peptidases (KLKs) as determined from a KLK pro-peptide fusion-protein system. That report described the activity profiles of 12 of the 15 mature KLKs versus the 15 different pro-KLK sequences. The missing profiles in the prior report, involving KLK9, 10, and 15, are now described. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis, mass spectrometry, and N-terminal sequence analyses show that KLK9 and 10 exhibit low hydrolytic activities towards all of the 15 pro-KLK sequences, while KLK15 exhibits significant activity towards both Arg- and Lys-containing KLK pro-sequences. The ability of KLK15 to activate pro-KLK8, 12, and 14 is confirmed using recombinant pro-KLK proteins, and shown to be significant for activation of pro-KLK8 and 14, but not 12. These additional data for KLK9, 10, and 15 now permit a completed KLK activome profile, using a KLK pro-peptide fusion-protein system, to be described. The results suggest that KLK15, once activated, can potentially feed back into additional pro-KLK activation pathways. Conversely, KLK9 and 10, once activated, are unlikely to participate in further pro-KLK activation pathways, although similar to KLK1 they may activate other bioactive peptides.