| 2010 |
KLK2 is the protease responsible for activating PSA (KLK3) zymogen, demonstrated in cell-based in vitro models (co-incubated cell clones), in vivo xenograft co-inoculation experiments, and PSA/KLK2 double-transgenic mice where double-transgenic animals produced more active PSA than single-transgenic animals. |
Cell-based co-incubation assays, subcutaneous xenograft co-inoculation, and prostate-targeted double-transgenic mouse models measuring free/total PSA ratios |
The Prostate |
High |
20058238
|
| 2010 |
KLK2 degrades IGFBP-3 into multiple small fragments with cleavage preferentially after Arg residues, consistent with its trypsin-like serine protease activity; cleavage sites were identified by mass spectrometry, and fragmentation was inhibited by KLK2-inhibiting peptides in a dose-dependent fashion. |
In vitro proteolysis assay with immunoblotting, two specific immunoassays (native vs. total IGFBP-3), mass spectrometry identification of cleavage sites, and KLK2-inhibiting peptide dose-response |
Biological chemistry |
High |
20180640
|
| 2008 |
KLK2 enzymatic (proteolytic) activity can be specifically inhibited by peptides developed against it; peptide stability was improved by cyclization, enabling development of in vivo-applicable KLK2 inhibitors. |
Peptide-based enzymatic activity assays, in vitro peptide inhibition, peptide cyclization for stability improvement |
Biological chemistry |
Medium |
18627344
|
| 2014 |
KLK2 promotes prostate cancer cell growth by cooperating with the AR coregulator ARA70 to enhance androgen receptor (AR) transactivation; KLK2 knockdown by siRNA caused increased apoptosis and G1-phase cell growth arrest, while KLK2 cDNA addition increased cell growth. |
KLK2 cDNA overexpression, KLK2-siRNA knockdown in LNCaP cells, colony formation assay, in vivo xenograft growth assay, AR transactivation reporter assay |
Tumour biology |
Medium |
24122203
|
| 2019 |
A KLK2-FGFR2 fusion protein (identified in metastatic prostate cancer) activates downstream FGFR signaling pathways, promotes enhanced cell migration, and induces profound morphological changes when expressed in NIH3T3 cells; the fusion is sensitive to selective FGFR inhibitors (AZD-4547, BGJ398, JNJ-42756943, TAS-120, Ponatinib) but not Dovitinib. |
Targeted RNA-sequencing to identify fusion, retroviral transduction of NIH3T3 cells, migration assays, Western blots for downstream FGFR signaling activation, drug sensitivity assays |
Prostate cancer and prostatic diseases |
Medium |
31043681
|
| 2024 |
KLK2 cleaves the extracellular domain of IL-10 receptor chain-2 (IL-10R2) at the sequence SYRIF (residues 58–63), reducing IL-10R2 surface expression on macrophages and blunting IL-10-mediated anti-inflammatory signaling (decreased inhibition of nitric oxide, TNF-α, and IL-12 p40). KLK2 is fully active at pH 8.0–8.2 and is strongly activated by sodium citrate and glycosaminoglycans. KLK3 did not show the same effects. |
FRET peptide library screening to identify optimal substrate (SYRIF), flow cytometry (FACS) to measure IL-10R2 surface expression on bone-marrow-derived macrophages after KLK2 treatment, functional inflammatory assays measuring nitric oxide, TNF-α, and IL-12 p40; comparison with KLK3 |
Biochemistry |
High |
39106042
|
| 2025 |
KLK2, previously considered a purely secreted serine protease with no cell-surface localization, has now been demonstrated to be expressed on the cell surface, making it targetable by antibody-based and other therapeutic modalities. |
Experimental demonstration of cell-surface localization (details attributed to a related article by Shen et al.) |
Clinical cancer research |
Low |
40924642
|
| 2026 |
KLK2 expression is strictly dependent on androgen receptor (AR) signaling, with coordinated binding of AR, FOXA1, and HOXB13 at the KLK2 locus and associated enhancer activation, as determined by epigenomic analysis of mCRPC patient samples; KLK2 expression is absent in neuroendocrine and AR-negative prostate cancer phenotypes. |
Transcriptomic and epigenomic profiling of 1095 mCRPC patient samples including ChIP/ATAC-seq-based analysis of AR/FOXA1/HOXB13 binding and enhancer activation, rapid autopsy cohort in situ studies |
Molecular cancer research |
Medium |
42189191
|
| 2002 |
Alternative splicing of KLK2 involving inclusion of intronic sequences adjacent to exon 1 produces a novel protein (hK2-linked molecule, K-LM) that shares only the signal peptide with KLK2; the mature K-LM protein is entirely different from kallikreins and shows androgen-regulated prostate-specific expression similar to KLK2. |
Identification of splice variant mRNAs by molecular cloning, protein characterization, and androgen-stimulation expression analysis |
The Journal of biological chemistry |
Medium |
11834722
|