A completed KLK activome profile: investigation of activation profiles of KLK9, 10, and 15.
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.
Yoon
Hyesook
H
Department of Chemistry and Biochemistry, Florida State University, Tallahassee, FL 32306-4300, USA.
Blaber
Sachiko I
SI
Debela
Mekdes
M
Goettig
Peter
P
Scarisbrick
Isobel A
IA
Blaber
Michael
M
D004587:Electrophoresis, Agar Gel; D020869:Gene Expression Profiling; D006801:Humans; D007610:Kallikreins / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism
D011993:Recombinant Fusion Proteins; C100936:KLK10 protein, human; C501608:KLK15 protein, human; C410801:KLK9 protein, human; D007610:Kallikreins