The human tissue Kallikrein gene family encodes 15 serine proteases. All Kallikreins share structural similarities including cysteine residues, a catalytic triad of His, Asp, and Ser residues, typically five coding exons, and varied intron phases. Kallikreins are predominantly secreted as inactive zymogens prior to activation by cleavage of an N-terminal peptide, and all function extracellularly. Kallikreins can be activated autocatalytically, via other Kallikreins, or additional proteases. While structurally similar, Kallikrein family members have distinct functions and have key roles in many physiological and pathological processes. Many human tissue Kallikreins also show promise as cancer biomarkers, which may facilitate earlier detection and characterization of many forms of cancer (Table 1).
Also known as prostate-specific antigen (PSA), Kallikrein 3 (KLK3) is a widely used clinical tumor marker that facilitates the diagnosis of prostate cancer. KLK3 is synthesized in the ductal and acinar epithelium of the prostate gland, and expression is often controlled by androgens. Secreted KLK3 is found in the seminal plasma in high concentrations. In comparison to the normal prostate gland, prostate cancer tissues allow significant amounts of KLK3 to enter circulation. In addition to its role as a prostate cancer marker, KLK3 also functions normally to liquefy seminal coagulum.
Recombinant Human Kallikrein 3/PSA
Kallikrein 4 (KLK4), also known as Prostase or enamel matrix serine protease 1 (EMPS1), is a recently identified member of the Kallikrein family. Normally secreted, it also appears to show nuclear localization. KLK4 is androgen-regulated and predominantly expressed in the basal cells of the normal prostate gland. It is overexpressed in cancers of the prostate and ovary, and it has been implicated as a prognostic factor. Potential physiological functions include the activation of pro-KLK3/PSA and pro-urokinase type plasminogen activator (uPA), and in enamel matrix protein remodeling.
Recombinant Human Kallikrein 4/Prostase
Kallikrein 5 (KLK5), also known as Kallikrein-Like 2 (KLK-L2) and Stratum Corneum Tryptic Enzyme (SCTE), is one of the lesser understood of the KLK family members. This is mainly due to the deficiency of suitable investigative reagents and methods. KLK5 is secreted and expressed in the salivary gland, esophagus, skin, and brain, and is highly enriched within hormonally regulated tissues including the breast, ovary, and testis. Due to its correlation between disease state and expression levels, investigative efforts are focusing on its role as a prognostic indicator for breast and ovarian cancers.
Recombinant Human Kallikrein 5
Several Kallikreins, including Kallikrein 8 (KLK8/Neuropsin), are expressed in the central nervous system (CNS). KLK8 is also found in endocrine-related tissue such as the ovary. Although KLK8 roles in the CNS continue to be elucidated, it may have importance in brain development, plasticity, and the stress response. Recent studies also show KLK8 in ovarian cancer tissue extracts, serum, and ascites fluid, indicating its potential as a marker and prognostic indicator for ovarian cancer.
Recombinant Human Kallikrein 8/Neuropsin
|Member||Alternate Names||Cancer Types|
|KLK1||Pancreatic/renal Kallikrein (hPRK)||Breast, Prostate|
|KLK2||Human glandular Kallikrein 1 (hGK-1)||Breast, Prostate|
|KLK3||Prostate-specific antigen (PSA)||Breast, Prostate|
|KLK4||Kallikrein-like 1 (KLK-L1) protein; Prostase; Enamel Matrix Serine Protease 1 (EMSP1)||Breast, Ovarian, Prostate|
|KLK5||Human Stratum Corneum Tryptic Enzyme (HSCTE); Kallikrein-like 2 (KLK-L2) protein||Breast, Ovarian, Prostate, Testicular|
|KLK6||Protease M; Neurosin; Zyme; Myelencephalon-specific Protease||Breast, Ovarian|
|KLK7||Human Stratum Corneum Chymotryptic Enzyme (HSCCE)||Ovarian|
|KLK8||Tumor-associated Differentially Expressed Gene-14 (TADG-14);
Neuropsin; Ovasin; Brain Serine Protease 1 (BSP1)
|KLK9||Kallikrein-like 3 (KLK-L3) protein||Ovarian|
|KLK10||Normal Epithelial Cell-Specific 1 (NES1) protein||Breast, Ovarian, Testicular|
|KLK11||Trypsin-like Serine Protease (TLSP); hippostasin||Ovarian, Prostate|
|KLK12||Kallikrein-like 5 (KLK-L5) protein||Breast|
|KLK13||Kallikrein-like 4 (KLK-L4) protein||Breast|
|KLK14||Kallikrein-like 6 (KLK-L6) protein||Breast, Ovarian, Testicular|
|KLK15||Breast, Ovarian, Prostate|
|Table 1. Human tissue Kallikreins as cancer markers.|