plasma kallikrein


Summary: A peptidohydrolytic enzyme that is formed from PREKALLIKREIN by FACTOR XIIA. It activates FACTOR XII; FACTOR VII; and PLASMINOGEN. It is selective for both ARGININE and to a lesser extent LYSINE bonds. EC

Top Publications

  1. Gozzo A, Nunes V, Carmona A, Nader H, von Dietrich C, Silveira V, et al. Glycosaminoglycans affect the action of human plasma kallikrein on kininogen hydrolysis and inflammation. Int Immunopharmacol. 2002;2:1861-5 pubmed
    Human plasma kallikrein (huPK) is a serine proteinase involved in many biological processes including those of the kallikrein-kinin system...
  2. Isawa H, Orito Y, Jingushi N, Iwanaga S, Morita A, Chinzei Y, et al. Identification and characterization of plasma kallikrein-kinin system inhibitors from salivary glands of the blood-sucking insect Triatoma infestans. FEBS J. 2007;274:4271-86 pubmed
    Two plasma kallikrein-kinin system inhibitors in the salivary glands of the kissing bug Triatoma infestans, designated triafestin-1 and triafestin-2, have been identified and characterized...
  3. Björkqvist J, Jämsä A, Renne T. Plasma kallikrein: the bradykinin-producing enzyme. Thromb Haemost. 2013;110:399-407 pubmed publisher
    Plasma prekallikrein is the liver-derived precursor of the trypsin-like serine protease plasma kallikrein (PK) and circulates in plasma bound to high molecular weight kininogen. The zymogen is converted to PK by activated factor XII...
  4. Feener E, Zhou Q, Fickweiler W. Role of plasma kallikrein in diabetes and metabolism. Thromb Haemost. 2013;110:434-41 pubmed publisher
    b>Plasma kallikrein (PK) is a serine protease generated from plasma prekallikrein, an abundant circulating zymogen expressed by the Klkb1 gene...
  5. Earl S, Richards R, Johnson L, Flight S, Anderson S, Liao A, et al. Identification and characterisation of Kunitz-type plasma kallikrein inhibitors unique to Oxyuranus sp. snake venoms. Biochimie. 2012;94:365-73 pubmed publisher
    ..inhibitors from the venoms of Oxyuranus scutellatus and Oxyuranus microlepidotus (Australian taipans) with plasma kallikrein inhibitory activity...
  6. Clermont A, Chilcote T, Kita T, Liu J, Riva P, Sinha S, et al. Plasma kallikrein mediates retinal vascular dysfunction and induces retinal thickening in diabetic rats. Diabetes. 2011;60:1590-8 pubmed publisher
    b>Plasma kallikrein (PK) has been identified in vitreous fluid obtained from individuals with diabetic retinopathy and has been implicated in contributing to retinal vascular dysfunction...
  7. Gozzo A, Nunes V, Cruz Silva I, Carmona A, Nader H, Faljoni Alario A, et al. Heparin modulation of human plasma kallikrein on different substrates and inhibitors. Biol Chem. 2006;387:1129-38 pubmed
    ..Human plasma kallikrein (huPK) is a proteolytic enzyme involved in intrinsic blood clotting, the kallikrein-kinin system and ..
  8. Abid K, Rochat B, Lassahn P, Stocklin R, Michalet S, Brakch N, et al. Kinetic study of neuropeptide Y (NPY) proteolysis in blood and identification of NPY3-35: a new peptide generated by plasma kallikrein. J Biol Chem. 2009;284:24715-24 pubmed publisher
    ..b>Plasma kallikrein at physiological concentrations converted NPY(3-36) into NPY(3-35)...
  9. Lilla J, Joshi R, Craik C, Werb Z. Active plasma kallikrein localizes to mast cells and regulates epithelial cell apoptosis, adipocyte differentiation, and stromal remodeling during mammary gland involution. J Biol Chem. 2009;284:13792-803 pubmed publisher plasmin by urokinase-type plasminogen activator (uPA), tissue-type plasminogen activator (tPA), and plasma kallikrein (PKal)...

More Information


  1. Schmaier A, McCrae K. The plasma kallikrein-kinin system: its evolution from contact activation. J Thromb Haemost. 2007;5:2323-9 pubmed
    The plasma kallikrein-kinin system consists of the proteins factor XII (FXII), prekallikrein (PK), and high molecular weight kininogen...
  2. Cruz Silva I, Gozzo A, Nunes V, Carmona A, Faljoni Alario A, Oliva M, et al. A proteinase inhibitor from Caesalpinia echinata (pau-brasil) seeds for plasma kallikrein, plasmin and factor XIIa. Biol Chem. 2004;385:1083-6 pubmed
    ..SDS-PAGE indicated a single polypeptide chain with a molecular mass of 20 kDa. CeKI inhibits human plasma kallikrein ( K i =3.1 nM), plasmin ( K i =0.18 nM), factor XIIa ( K i =0.18 nM), trypsin ( K i =21...
  3. Selvarajan S, Lund L, Takeuchi T, Craik C, Werb Z. A plasma kallikrein-dependent plasminogen cascade required for adipocyte differentiation. Nat Cell Biol. 2001;3:267-75 pubmed
    Here we show that plasma kallikrein (PKal) mediates a plasminogen (Plg) cascade in adipocyte differentiation...
  4. Lund L, Green K, Stoop A, Ploug M, Almholt K, Lilla J, et al. Plasminogen activation independent of uPA and tPA maintains wound healing in gene-deficient mice. EMBO J. 2006;25:2686-97 pubmed
    ..In vivo administration of a plasma kallikrein (pKal)-selective form of the serine protease inhibitor ecotin exacerbates the healing impairment of uPA;tPA ..
  5. Fink E, Bhoola K, Snyman C, Neth P, Figueroa C. Cellular expression of plasma prekallikrein in human tissues. Biol Chem. 2007;388:957-63 pubmed
    ..Here we demonstrate by immunohistochemical studies that PPK or plasma kallikrein (PK) is localised in cells of different embryologically derived human tissues...
  6. Feener E. Plasma kallikrein and diabetic macular edema. Curr Diab Rep. 2010;10:270-5 pubmed publisher
    Recent proteomic studies have identified components of the kallikrein kinin system, including plasma kallikrein, factor XII, and kininogen, in vitreous obtained from individuals with advanced diabetic retinopathy...
  7. Stolz L, Horn P. Ecallantide: a plasma kallikrein inhibitor for the treatment of acute attacks of hereditary angioedema. Drugs Today (Barc). 2010;46:547-55 pubmed publisher
    ..Ecallantide is a novel, specific and potent inhibitor of plasma kallikrein that was recently approved in the United States for the treatment of acute attacks of HAE in patients aged ..
  8. Liu J, Gao B, Clermont A, Blair P, Chilcote T, Sinha S, et al. Hyperglycemia-induced cerebral hematoma expansion is mediated by plasma kallikrein. Nat Med. 2011;17:206-10 pubmed publisher
    ..diabetic rats and mice compared to nondiabetic controls and that this augmented expansion is ameliorated by plasma kallikrein (PK) inhibition or deficiency...
  9. Bird J, Smith P, Wang X, Schumacher W, Barbera F, Revelli J, et al. Effects of plasma kallikrein deficiency on haemostasis and thrombosis in mice: murine ortholog of the Fletcher trait. Thromb Haemost. 2012;107:1141-50 pubmed publisher
    b>Plasma kallikrein is a multifunctional serine protease involved in contact activation of coagulation...
  10. Shariat Madar Z, Mahdi F, Schmaier A. Assembly and activation of the plasma kallikrein/kinin system: a new interpretation. Int Immunopharmacol. 2002;2:1841-9 pubmed
    Understanding the importance and physiologic activity of the plasma kallikrein/kinin system (KKS) has been thwarted by the absence of an inclusive theory for its assembly and activation...
  11. Almeida S, Barros C, Moraes M, Russo F, Haro A, Rosa T, et al. Plasma Kallikrein and Angiotensin I-converting enzyme N- and C-terminal domain activities are modulated by the insertion/deletion polymorphism. Neuropeptides. 2010;44:139-43 pubmed publisher
    ..b>Plasma kallikrein activity was measured using Z-Phe-Arg-AMC as substrate and inhibited by selective plasma kallikrein ..
  12. Tang J, Yu C, Williams S, Springman E, Jeffery D, Sprengeler P, et al. Expression, crystallization, and three-dimensional structure of the catalytic domain of human plasma kallikrein. J Biol Chem. 2005;280:41077-89 pubmed
    b>Plasma kallikrein is a serine protease that has many important functions, including modulation of blood pressure, complement activation, and mediation and maintenance of inflammatory responses...
  13. Storini C, Bergamaschini L, Gesuete R, Rossi E, Maiocchi D, De Simoni M. Selective inhibition of plasma kallikrein protects brain from reperfusion injury. J Pharmacol Exp Ther. 2006;318:849-54 pubmed
    We have studied the effect of DX-88, a selective recombinant inhibitor of human plasma kallikrein, in transient or permanent focal brain ischemia (with or without reperfusion, respectively) induced in C57BL/6 mice...
  14. Flight S, Johnson L, Trabi M, Gaffney P, Lavin M, de Jersey J, et al. Comparison of textilinin-1 with aprotinin as serine protease inhibitors and as antifibrinolytic agents. Pathophysiol Haemost Thromb. 2005;34:188-93 pubmed
    ..When equimolar concentrations of enzyme and aprotinin were pre-incubated, plasmin was inhibited 100%, plasma kallikrein 58%, and tissue kallikrein 99%...
  15. Portelli M, Siedlinski M, Stewart C, Postma D, Nieuwenhuis M, Vonk J, et al. Genome-wide protein QTL mapping identifies human plasma kallikrein as a post-translational regulator of serum uPAR levels. FASEB J. 2014;28:923-34 pubmed publisher
    ..In these cohorts, a genome-wide association study of serum scuPAR levels identified a human plasma kallikrein gene (KLKB1) promoter polymorphism (rs4253238) associated with serum scuPAR levels in a control/asthma ..
  16. Campbell D, Dixon B, Kladis A, Kemme M, Santamaria J. Activation of the kallikrein-kinin system by cardiopulmonary bypass in humans. Am J Physiol Regul Integr Comp Physiol. 2001;281:R1059-70 pubmed
    ..Aprotinin administration prevented activation of the KKS. The changes in circulating kinin and kallikrein levels indicate activation of both the plasma and tissue KKS during activation of the contact system by CPB...
  17. Briseid K, Johannesen S. Kallikrein modification with affinity to IgG present in higher amounts than normal in plasma from patients with Crohn's disease. Scand J Clin Lab Invest. 2003;63:425-9 pubmed
    ..An IgG removal procedure removed all modified kallikrein, and did not affect ordinary kallikrein levels. ..
  18. Kolte D, Bryant J, Holsworth D, Wang J, Akbari P, Gibson G, et al. Biochemical characterization of a novel high-affinity and specific plasma kallikrein inhibitor. Br J Pharmacol. 2011;162:1639-49 pubmed publisher
    ..The aim of this study was to investigate whether our novel plasma kallikrein inhibitor abolishes kallikrein-mediated generation of BK from HK and subsequent BK-induced NO and PGI(2) ..
  19. Lima A, Alves F, Angelo P, Andrade D, Blaber S, Blaber M, et al. S(1)' and S(2)' subsite specificities of human plasma kallikrein and tissue kallikrein 1 for the hydrolysis of peptides derived from the bradykinin domain of human kininogen. Biol Chem. 2008;389:1487-94 pubmed publisher
    The S(1)' and S(2)' subsite specificities of human tissue kallikrein 1 (KLK1) and human plasma kallikrein (HPK) were examined with the peptide series Abz-GFSPFRXSRIQ-EDDnp and Abz-GFSPFRSXRIQ-EDDnp [X=natural amino acids or S(PO(3)H(2))]...
  20. Saito A. Plasma kallikrein is activated on dermatan sulfate and cleaves factor H. Biochem Biophys Res Commun. 2008;370:646-50 pubmed publisher
    ..gel filtration and hydroxyapatite chromatography, and the amidase-active protein was identified to be plasma kallikrein by mass spectrometry...
  21. Dunn B, BUNGERT J. Two hands (or four) are better than one. Nat Biotechnol. 2003;21:1019-21 pubmed
  22. González Y, Tanaka A, Hirata I, del Rivero M, Oliva M, Araujo M, et al. Purification and partial characterization of human neutrophil elastase inhibitors from the marine snail Cenchritis muricatus (Mollusca). Comp Biochem Physiol A Mol Integr Physiol. 2007;146:506-13 pubmed
    ..2 and 1.6 nM, respectively. In addition, trypsin and pancreatic elastase were also inhibited, but not plasma kallikrein or thrombin. CmPI-I and CmPI-II are the first human neutrophil elastase inhibitors described in a mollusk.
  23. Simões H, Asano R, Sales M, Browne R, Arsa G, Motta Santos D, et al. Type 2 diabetes elicits lower nitric oxide, bradykinin concentration and kallikrein activity together with higher DesArg(9)-BK and reduced post-exercise hypotension compared to non-diabetic condition. PLoS ONE. 2013;8:e80348 pubmed publisher
    This study compared the plasma kallikrein activity (PKA), bradykinin concentration (BK), DesArg(9)-BK production, nitric oxide release (NO) and blood pressure (BP) response after moderate-intensity aerobic exercise performed by ..
  24. Stoop A, Craik C. Engineering of a macromolecular scaffold to develop specific protease inhibitors. Nat Biotechnol. 2003;21:1063-8 pubmed
    ..The efficacy of these libraries was demonstrated against the serine protease plasma kallikrein (Pkal)...
  25. Syrtlanova E, Gil mutdinova L. [The use of moxonidine in patients with essential hypertension combined with metabolic syndrome]. Kardiologiia. 2003;43:33-5 pubmed
  26. Colman R. Plasma and tissue kallikrein in arthritis and inflammatory bowel disease. Immunopharmacology. 1999;43:103-8 pubmed
    To ascertain the participation of the plasma kallikrein-kinin system (KKS) in arthritis and inflammatory bowel disease, we used two rat models resembling rheumatoid arthritis and Crohn's disease...
  27. Baeriswyl V, Heinis C. Phage selection of cyclic peptide antagonists with increased stability toward intestinal proteases. Protein Eng Des Sel. 2013;26:81-9 pubmed publisher
    ..Panning with the therapeutic target plasma kallikrein yielded potent inhibitors (K(i)s between 5...
  28. Zacharieva S, Atanassova I, Natchev E, Orbetzova M, Tzingilev D. Effect of short-term losartan treatment in patients with primary aldosteronism and essential hypertension. Methods Find Exp Clin Pharmacol. 2001;23:153-6 pubmed
    ..The variations in KA could be due to hemodynamic changes. VEGF is not likely to be involved in the action of losartan. ..
  29. Tsuda Y, Tada M, Wanaka K, Okamoto U, Hijikata Okunomiya A, Okamoto S, et al. Structure-inhibitory activity relationship of plasmin and plasma kallikrein inhibitors. Chem Pharm Bull (Tokyo). 2001;49:1457-63 pubmed
    ..with a moiety bearing a hydrophobic group gave the proper affinity of the inhibitor to both plasmin (PL) and plasma kallikrein (PK)...
  30. Nieziołek M, Kot M, Pyka K, Mak P, Kozik A. Properties of chemically oxidized kininogens. Acta Biochim Pol. 2003;50:753-63 pubmed
    ..However, virtually no kinin could be formed by human plasma kallikrein from NCS-modified HK...
  31. Ishii K, Otsuka T, Iguchi K, Usui S, Yamamoto H, Sugimura Y, et al. Evidence that the prostate-specific antigen (PSA)/Zn2+ axis may play a role in human prostate cancer cell invasion. Cancer Lett. 2004;207:79-87 pubmed
    ..Loss of inhibition of the proteolytic activity of PSA by Zn(2+) in prostate tumors could contribute to invasion. ..
  32. Kondratovich A, Pokhilko A, Ataullakhanov F. Spatiotemporal dynamics of contact activation factors of blood coagulation. Biochim Biophys Acta. 2002;1569:86-104 pubmed
    ..The maximum concentration of the active factors was estimated at 2 x 10(8) molecules per mm(2) at the glass surface (irrespective of stirring). At the plastic surface, this value was 15--30 times lower. ..
  33. Nagaoka M, Kouyoumdjian M, Borges D. Hepatic clearance of tissue-type plasminogen activator and plasma kallikrein in experimental liver fibrosis. Liver Int. 2003;23:476-83 pubmed
    We have previously shown that tissue-type plasminogen activator (tPA) and rat plasma kallikrein (RPK) share a common, but not unique, pathway for liver clearance...
  34. Schmaier A. The contact activation and kallikrein/kinin systems: pathophysiologic and physiologic activities. J Thromb Haemost. 2016;14:28-39 pubmed publisher
    ..The KKS is an inflammatory response mechanism. Targeting their activation through FXIIa or plasma kallikrein inhibition when blood interacts with the artificial surfaces of modern interventional medicine or in acute ..
  35. Banerji A, Busse P, Shennak M, Lumry W, Davis Lorton M, Wedner H, et al. Inhibiting Plasma Kallikrein for Hereditary Angioedema Prophylaxis. N Engl J Med. 2017;376:717-728 pubmed publisher
    ..inhibitor deficiency is characterized by recurrent, unpredictable swelling episodes caused by uncontrolled plasma kallikrein generation and excessive bradykinin release resulting from cleavage of high-molecular-weight kininogen...
  36. Dellalibera Joviliano R, Joviliano E, Evora P. Determination of kininogens levels and kallikrein/kininase II activities in patients with thromboangiitis obliterans. Scand J Immunol. 2010;72:128-33 pubmed publisher
    Some components of the kinin system such as plasma kallikrein levels, the activities of tissue kallikrein (including saliva) and kininase II and the concentrations of kininogen fractions (low-molecular weight/LKg and high-molecular ..
  37. Huang W, Wan X, Zhang S. A novel chromogenic peptide for prekallikrein/kallikrein determination. Clin Lab. 2009;55:106-13 pubmed
    ..A sensitive and reliable chromogenic substrate assay for human plasma prekallikrein was developed by using this novel substrate. ..
  38. Griesbacher T, Rainer I, Tiran B, Fink E, Lembeck F, Peskar B. Mechanism of kinin release during experimental acute pancreatitis in rats: evidence for pro- as well as anti-inflammatory roles of oedema formation. Br J Pharmacol. 2003;139:299-308 pubmed
    ..This increase was absent in rats that were pretreated with icatibant. 4 During pancreatitis, t-KK-like and plasma kallikrein (p-KK)-like activity in the pancreas, as well as trypsinogen activation peptide (TAP) increased ..
  39. Gozzo A, Nunes V, Nader H, Dietrich C, Carmona A, Sampaio M, et al. Glycosaminoglycans affect the interaction of human plasma kallikrein with plasminogen, factor XII and inhibitors. Braz J Med Biol Res. 2003;36:1055-9 pubmed
    Human plasma kallikrein, a serine proteinase, plays a key role in intrinsic blood clotting, in the kallikrein-kinin system, and in fibrinolysis...
  40. Blat Y, Seiffert D. A renaissance for the contact system in blood coagulation?. Thromb Haemost. 2008;99:457-60 pubmed publisher
  41. Vonnahme K, Fernando S, Ross J, Ashworth M, DeSilva U, Malayer J, et al. Porcine endometrial expression of kininogen, factor XII, and plasma kallikrein in cyclic and pregnant gilts. Biol Reprod. 2004;70:132-8 pubmed
    ..The possible involvement of plasma kallikrein and Factor XII, activators of the kallikrein-kininogen-kinin system, were evaluated through analysis of gene ..
  42. Shia S, Stamos J, Kirchhofer D, Fan B, Wu J, Corpuz R, et al. Conformational lability in serine protease active sites: structures of hepatocyte growth factor activator (HGFA) alone and with the inhibitory domain from HGFA inhibitor-1B. J Mol Biol. 2005;346:1335-49 pubmed
    ..We find that HGFA, matriptase, hepsin, plasma kallikrein and trypsin are potently inhibited, and use the complex structure to rationalize the structural basis of ..
  43. Rosatelli T, Roselino A, Dellalibera Joviliano R, Reis M, Donadi E. Increased activity of plasma and tissue kallikreins, plasma kininase II and salivary kallikrein in pemphigus foliaceus (fogo selvagem). Br J Dermatol. 2005;152:650-7 pubmed
    ..levels of high-molecular-weight kininogen (HK) and low-molecular-weight kininogen (LK), and the activity of plasma kallikrein, tissue kallikrein and kininase II in plasma of patients with PF presenting with Nikolsky's sign...
  44. Chee J, Naran A, Misso N, Thompson P, Bhoola K. Expression of tissue and plasma kallikreins and kinin B1 and B2 receptors in lung cancer. Biol Chem. 2008;389:1225-33 pubmed publisher
    Tissue kallikrein (hK1) and plasma kallikrein (PK, hKB1) are serine proteases that produce biologically active kinin peptides from endogenous kininogen substrates...
  45. Teno N, Otsubo T, Gohda K, Wanaka K, Sueda T, Ikeda K, et al. Synthesis and evaluation of tripeptidic plasmin inhibitors with nitrile as warhead. J Pept Sci. 2012;18:620-5 pubmed publisher
    ..were prepared and evaluated for their inhibitory activities against plasmin and other serine proteases, plasma kallikrein and urokinase...
  46. Cerf M, Raidoo D. Immunolocalization of plasma kallikrein in human brain. Metab Brain Dis. 2000;15:315-23 pubmed
    b>Plasma kallikrein (PK) is a cofactor in blood coagulation and modulates inflammation through the release of bradykinin...
  47. Pathak M, Wong S, Dreveny I, Emsley J. Structure of plasma and tissue kallikreins. Thromb Haemost. 2013;110:423-33 pubmed publisher
    ..proteases and examine the molecular mechanisms of zymogen activation and substrate recognition focusing on plasma kallikrein (PK) and tissue kallikrein (KLK1) cleavage of kininogens...
  48. Oliva M, Mendes C, Santomauro Vaz E, Juliano M, Mentele R, Auerswald E, et al. Bauhinia bauhinioides plasma kallikrein inhibitor: interaction with synthetic peptides and fluorogenic peptide substrates related to the reactive site sequence. Curr Med Chem. 2001;8:977-84 pubmed
    ..The main eluted peak inhibits trypsin (Ki = 0.6 nM), plasma kallikrein (Ki = 0.35 nM), plasmin (Ki = 33...
  49. Saito A. Diversity of human plasma protein C inhibitor. Thromb Res. 2012;130:661-6 pubmed publisher
    ..The heterogeneity of the protein C inhibitor species was not due to glycosylation or phosphorylation. ..
  50. Koumandou V, Scorilas A. Evolution of the plasma and tissue kallikreins, and their alternative splicing isoforms. PLoS ONE. 2013;8:e68074 pubmed publisher
    Kallikreins are secreted serine proteases with important roles in human physiology. Human plasma kallikrein, encoded by the KLKB1 gene on locus 4q34-35, functions in the blood coagulation pathway, and in regulating blood pressure...
  51. Yoon H, Blaber S, Evans D, Trim J, Juliano M, Scarisbrick I, et al. Activation profiles of human kallikrein-related peptidases by proteases of the thrombostasis axis. Protein Sci. 2008;17:1998-2007 pubmed publisher
    ..The results show that proteases of the thrombostasis family can efficiently activate specific pro-KLKs, demonstrating the potential for important regulatory interactions between these two major protease families. ..
  52. Oliva M, Sampaio M. Action of plant proteinase inhibitors on enzymes of physiopathological importance. An Acad Bras Cienc. 2009;81:615-21 pubmed
    ..Although proteins from this group share high structural similarity, they present differences in proteinase inhibition, explored in studies using diverse biological models. ..
  53. Dulinski R, Suder P, Guevara Lora I, Rapała Kozik M, Potempa J, Silberring J, et al. Attenuated kinin release from human neutrophil elastase-pretreated kininogens by tissue and plasma kallikreins. Biol Chem. 2003;384:929-37 pubmed human urinary kallikrein (tissue-type) and also significantly quenches the kinin release from HK by plasma kallikrein. Studies with synthetic model heptadecapeptide substrates, ISLMKRPPGFSPFRSSR and SLMKRPPGFSPFRSSRI, ..