Kallikreins are a subgroup of
serine proteases,
enzymes capable of cleaving peptide bonds in proteins. In humans,
plasma kallikrein (encoded by KLKB1 gene) has no known
paralogue, while tissue kallikrein-related peptidases (KLKs) encode a family of fifteen closely related serine proteases. These genes are localised to chromosome
19q13, forming the largest contiguous cluster of proteases within the human genome. Kallikreins are responsible for the coordination of various physiological functions including
blood pressure,
semen liquefaction and
skin desquamation.
Occurrence
In 1934,
Eugen Werle reported finding a substance in the
pancreas of humans and various animals in such large amounts that the pancreas could be taken for its site of origin. He named it kallikrein, by derivation from the Greek word for pancreas. Since then, similar enzymes have been found in the biological fluids of humans and other mammals, as well as in some snake venoms.[1]
Venom
The caterpillar known as Lagoa crispata contains poison glands attached to hypodermic spines, which produce and inject venom that has been characterized as kallikrein in nature.[2]
The venom of
solenodons and some
shrews like the
northern short-tailed shrew consist of multiple copies of kallikrein 1 (KLK1) serine proteases.[3] KLK1 are very similar to serine protease found in venomous snakes like vipers, and have evolved in parallel from a common toxin precursor,[4] which cause hypotensive effects in vivo.[5]
Plasma kallikrein
The KLKB1 gene encoding
plasma kallikrein is located on chromosome
4q34-35. It is synthesised as an inactive precursor,
prekallikrein, which must undergo proteolytic processing to become activated. This is facilitated by
factor XII,
PRCP or other stimuli.[citation needed]
Plasma kallikrein liberates
kinins (
bradykinin and
kallidin) from the
kininogens,[6][7] peptides responsible for the regulation of blood pressure and activation of inflammation. It is also capable of generating
plasmin from
plasminogen:
Distinct from plasma kallikrein, tissue kallikreins (KLKs) are expressed throughout the human body and perform various physiological roles. As some kallikreins are able to catalyse the activation of other kallikreins, several cascades involving these proteases have been implicated in the regulation of homeostatic functions.[citation needed]
Function
Similar to KLKB1, three tissue kallikreins
KLK1,
KLK2 and
KLK12 also participate in regulation of blood pressure via the activation of bradykinin.[8] KLK2,
KLK3,
KLK4,
KLK5 and
KLK14 are expressed in the prostate and are thought to be responsible for regulating semen liquefaction through hydrolysis of
semenogelin.[9][10]Desquamation of the skin is likely controlled by KLK5,
KLK7 and KLK14, which are expressed in the outermost layer of the epidermis and cleave cellular adhesion proteins.[11] Additionally,
KLK6 and
KLK8 are associated with neuronal plasticity in the central nervous system.[12]
^Raspi G (September 1996). "Kallikrein and kallikrein-like proteinases: purification and determination by chromatographic and electrophoretic methods". Journal of Chromatography. B, Biomedical Applications. 684 (1–2): 265–287.
doi:
10.1016/0378-4347(96)00144-2.
PMID8906477.
^Lamdin JM, Howell DE, Kocan KM, Murphey DR, Arnold DC, Fenton AW, et al. (September 2000). "The venomous hair structure, venom and life cycle of Lagoa crispata, a puss caterpillar of Oklahoma". Toxicon. 38 (9): 1163–1189.
doi:
10.1016/s0041-0101(99)00195-6.
PMID10736472.
^Kita M, Okumura Y, Ohdachi SD, Oba Y, Yoshikuni M, Nakamura Y, et al. (February 2005). "Purification and characterisation of blarinasin, a new tissue kallikrein-like protease from the short-tailed shrew Blarina brevicauda: comparative studies with blarina toxin". Biological Chemistry. 386 (2): 177–182.
doi:
10.1515/BC.2005.022.
hdl:2115/7398.
PMID15843162.
S2CID2884850.
^Ovaere P, Lippens S, Vandenabeele P, Declercq W (September 2009). "The emerging roles of serine protease cascades in the epidermis". Trends in Biochemical Sciences. 34 (9): 453–463.
doi:
10.1016/j.tibs.2009.08.001.
PMID19726197.
^Borgoño CA, Diamandis EP (November 2004). "The emerging roles of human tissue kallikreins in cancer". Nature Reviews. Cancer. 4 (11): 876–890.
doi:
10.1038/nrc1474.
PMID15516960.
S2CID382797.