TY - JOUR
T1 - A completed KLK activome profile
T2 - Investigation of activation profiles of KLK9, 10, and 15
AU - Yoon, Hyesook
AU - Blaber, Sachiko I.
AU - Debela, Mekdes
AU - Goettig, Peter
AU - Scarisbrick, Isobel A.
AU - Blaber, Michael
N1 - Funding Information:
This work was supported by NIH grant 1R15NS057771-01 (M.B.), and National Multiple Sclerosis Society grants PP1113 (M.B.) and RG3367 (I.A.S).
PY - 2009/4/1
Y1 - 2009/4/1
N2 - 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.
AB - 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.
KW - Activation cascade
KW - Activome
KW - Kallikrein
KW - Kallikrein-related peptidases (KLKs)
KW - Protease
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U2 - 10.1515/BC.2009.026
DO - 10.1515/BC.2009.026
M3 - Article
C2 - 19090718
AN - SCOPUS:64849117485
SN - 1431-6730
VL - 390
SP - 373
EP - 377
JO - Biological Chemistry
JF - Biological Chemistry
IS - 4
ER -