| 词条 | Kallikrein |
| 释义 |
Kallikreins are a subgroup of serine proteases, enzymes capable of cleaving peptide bonds in proteins. In humans, plasma kallikrein (KLKB1) 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. OccurrenceEugen Werle reported in 1934 finding a substance in the pancreas of humans and various animals in such great 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]VenomThe 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 short-tailed shrews produce kallikrein-like proteins in their venom.[3] Plasma kallikreinThe 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. Plasma kallikrein liberates kinins (bradykinin and kallidin) from the kininogens,[4][5] peptides responsible for the regulation of blood pressure and activation of inflammation. It is also capable of generating plasmin from plasminogen: Structure{{Further|Prekallikrein#Structure}}Kallikrein is homologous to factor XI and consists of four apple domains and one serine protease domain. Tissue kallikreinsDistinct 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. FunctionSimilar to KLKB1, three tissue kallikreins KLK1, KLK2 and KLK12 also participate in regulation of blood pressure via the activation of bradykinin.[6] KLK2, KLK3, KLK4, KLK5 and KLK14 are expressed in the prostate and are thought to be responsible for regulating semen liquefaction through hydrolysis of seminogelin.[7][8] 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.[9] Additionally, KLK6 and KLK8 are associated with neuronal plasticity in the central nervous system.[10] GenesThere are 15 known human tissue kallikreins: KLK1, KLK2, KLK3, KLK4, KLK5, KLK6, KLK7, KLK8, KLK9, KLK10, KLK11, KLK12, KLK13, KLK14, KLK15 Clinical significanceKallikrein-related peptidases are targets of active investigation by drug researchers as possible biomarkers for cancer.[11][12] Prostate-specific antigen (PSA; hk3, human kallikrein gene 3) and human glandular kallikrein (hK2) are used as tumor markers for prostate cancer. Ecallantide is an FDA-approved drug that inhibits kallikrein and can be used for managing Hereditary Angioedema. The excretion of KLK9 in urine has been associated to cardiac hypertrophy and aorta wall thickness in animal models [13] See also
References1. ^{{cite journal |author=Raspi G |title=Kallikrein and kallikrein-like proteinases: purification and determination by chromatographic and electrophoretic methods |journal=J. Chromatogr. B |volume=684 |issue=1–2 |pages=265–87 |date=September 1996 |pmid=8906477 |url=http://www.icb.ufmg.br/prodabi/prodabi5/homepages/liza/artigos/review2.pdf |doi=10.1016/0378-4347(96)00144-2}} 2. ^{{cite journal |vauthors=Lamdin JM, Howell DE, Kocan KM, etal |title=The venomous hair structure, venom and life cycle of Lagoa crispata, a puss caterpillar of Oklahoma |journal=Toxicon |volume=38 |issue=9 |pages=1163–89 |date=September 2000 |pmid=10736472 |url=http://linkinghub.elsevier.com/retrieve/pii/S0041-0101(99)00195-6 |doi=10.1016/s0041-0101(99)00195-6}} 3. ^{{cite journal | vauthors = Kita M, Okumura Y, Ohdachi SD, Oba Y, Yoshikuni M, Nakamura Y, Kido H, Uemura D | title = Purification and characterisation of blarinasin, a new tissue kallikrein-like protease from the short-tailed shrew Blarina brevicauda: comparative studies with blarina toxin | journal = Biological Chemistry | volume = 386 | issue = 2 | pages = 177–82 |date=February 2005 | doi = 10.1515/BC.2005.022 | pmid = 15843162}} 4. ^{{cite journal |vauthors=Bhoola KD, Figueroa CD, Worthy K |title=Bioregulation of kinins: kallikreins, kininogens, and kininases |journal=Pharmacol. Rev. |volume=44 |issue=1 |pages=1–80 |date=March 1992 |pmid=1313585 |url=http://pharmrev.aspetjournals.org/cgi/pmidlookup?view=long&pmid=1313585}} 5. ^{{cite book|author1=Stefan Offermanns|author2=Walter Rosenthal|title=Encyclopedia of Molecular Pharmacology|url=https://books.google.com/books?id=iwwo5gx8aX8C&pg=PA673|accessdate=11 December 2010|year=2008|publisher=Springer|isbn=978-3-540-38916-3|pages=673–}} 6. ^{{cite journal |vauthors=Giusti B, Serratì S, Margheri F, Papucci L, Rossi L, Poggi F, Magi A, Del Rosso A, Cinelli M, Guiducci S, Kahaleh B, Matucci-Cerinic M, Abbate R, Fibbi G, Del Rosso M | title = The antiangiogenic tissue kallikrein pattern of endothelial cells in systemic sclerosis | journal = Arthritis Rheum | volume = 52 | issue = 11 | pages = 3618–28 |date=November 2005 | pmid = 16255054 | pmc = | doi =10.1002/art.21383 }} 7. ^{{cite journal |vauthors=Michael IP, Pampalakis G, Mikolajczyk SD, Malm J, Sotiropoulou G, Diamandis EP | title = Human tissue kallikrein 5 is a member of a proteolytic cascade pathway involved in seminal clot liquefaction and potentially in prostate cancer progression. | journal = J Biol Chem | volume = 281 | issue = 18 | pages = 12743–50 |date=May 2006 | pmid = 16517595 | pmc = | doi = 10.1074/jbc.M600326200}} 8. ^{{cite journal |vauthors=Emami N, Diamandis EP | title = Human kallikrein-related peptidase 14 (KLK14) is a new activator component of the KLK proteolytic cascade. Possible function in seminal plasma and skin | journal = J Biol Chem | volume = 283 | issue = 6 | pages = 3031–41 |date=February 2008 | pmid = 18056261 | pmc = | doi = 10.1074/jbc.M707253200}} 9. ^{{cite journal |vauthors=Ovaere P, Lippens S, Vandenabeele P, Declercq W | title = The emerging roles of serine protease cascades in the epidermis | journal = Trends Biochem Sci | volume = 34 | issue = 9 | pages = 453–63 |date=August 2009 | pmid = 19726197 | pmc = | doi = 10.1016/j.tibs.2009.08.001}} 10. ^{{cite journal |vauthors=Tamura H, Ishikawa Y, Hino N, Maeda M, Yoshida S, Kaku S, Shiosaka S | title = Neuropsin is essential for early processes of memory acquisition and Schaffer collateral long-term potentiation in adult mouse hippocampus in vivo | journal = J Physiol | volume = 570| issue = 3 | pages = 541–51 |date=February 2006 | pmid = 16308352 | pmc = 1479887| doi =10.1113/jphysiol.2005.098715 }} 11. ^{{cite journal |vauthors=Borgoño CA, Diamandis EP |title=The emerging roles of human tissue kallikreins in cancer |journal=Nat. Rev. Cancer |volume=4 |issue=11 |pages=876–90 |date=November 2004 |pmid=15516960 |doi=10.1038/nrc1474 }} 12. ^{{cite journal |vauthors=Diamandis EP, Yousef GM |title=Human tissue kallikreins: a family of new cancer biomarkers |journal=Clin. Chem. |volume=48 |issue=8 |pages=1198–205 |date=August 2002 |pmid=12142373 |url=http://www.clinchem.org/cgi/pmidlookup?view=long&pmid=12142373}} 13. ^{{Cite journal|last=Blázquez-Medela|first=Ana M.|last2=García-Sánchez|first2=Omar|last3=Quirós|first3=Yaremi|last4=Blanco-Gozalo|first4=Victor|last5=Prieto-García|first5=Laura|last6=Sancho-Martínez|first6=Sandra M.|last7=Romero|first7=Miguel|last8=Duarte|first8=Juan M.|last9=López-Hernández|first9=Francisco J.|date=2015-10-01|title=Increased Klk9 Urinary Excretion Is Associated to Hypertension-Induced Cardiovascular Damage and Renal Alterations|journal=Medicine|volume=94|issue=41|pages=e1617|doi=10.1097/MD.0000000000001617|issn=1536-5964|pmc=4616806|pmid=26469898}} External links
3 : EC 3.4.21|Kinin–kallikrein system|Urticaria and angioedema |
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