Human tissue kallikreins 3 and 5 can act as plasminogen activator releasing active plasmin

Souza, Lucas R. de; Melo, Pollyana M.S.; Paschoalin, Thaysa; Carmona, Adriana K.; Kondo, Márcia Y.; Hirata, Izaura Yoshico; Blaber, Michael; Tersariol, Ivarne L.S.; Takatsuka, Joyce; Juliano, María A.; Juliano, Luiz; Gomes, Roseli Aparecida da Silva; Puzer, Luciano

doi:10.1016/j.bbrc.2013.03.001

Cited by 16 publications

(11 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This abolished virus replication ex vivo , thereby confirming the importance of KLK13 during infection. KLK13 is thought to be secreted and membrane-bound( 82, 83 ).…”

Section: Discussionmentioning

confidence: 99%

Kallikrein 13: a new player in coronaviral infections

Milewska

Falkowski

Kalińska

et al. 2020

Preprint

View full text Add to dashboard Cite

35Human coronavirus HKU1 (HCoV-HKU1) is associated with respiratory disease and is 36 prevalent worldwide, but in vitro model for virus replication is lacking. Interaction between the 37 coronaviral spike (S) protein and its receptor is the major determinant of virus tissue and host 38 specificity, but virus entry is a complex process requiring a concerted action of multiple cellular 39 elements. Here, we show that KLK13 is required for the infection of the human respiratory 40 epithelium and is sufficient to mediate the entry of HCoV-HKU1 to non-permissive RD cells. 41 We also demonstrated HCoV-HKU1 S protein cleavage by KLK13 in the S1/S2 region, proving 42 that KLK13 is the priming enzyme for this virus. Summarizing, we show for the first time that 43 protease distribution and specificity predetermines the tissue and cell specificity of the virus 44 and may also regulate interspecies transmission. It is also of importance that presented data may 45 be relevant for the emerging coronaviruses, including SARS-CoV-2 and may help to understand 46 the differences in their zoonotic potential. : bioRxiv preprint 48Coronaviruses are the largest group within the order Nidovirales. Mainly, they cause 49 respiratory and enteric diseases in humans and animals, but some can cause more serious 50 conditions such as hepatitis, peritonitis, or neurological disease. Seven coronaviruses infect 51 humans, four of which (human coronavirus [HCoV]-229E, HCoV-NL63, HCoV-OC43, and 52 HCoV-HKU1) cause relatively mild upper and lower respiratory tract disease and two (SARS-53 CoV and MERS-CoV) are associated with severe, life-threatening respiratory infections and 54 multiorgan failure (1-6). Furthermore, in December 2019 a novel coronavirus SARS-CoV-2 55 emerged in Hubei province, China, causing pneumonia. To date, almost 90,000 cases were 56 identified and 3,000 patients died worldwide. 57 Coronaviral infection is initiated by interaction between the trimeric spike (S) protein 58 and its receptor, which is expressed on the surface of the susceptible cell. A number of adhesion 59 and entry receptors have been described for coronaviruses. For example, HCoV-229E (similar 60 to many other alphacoronaviruses) utilizes aminopeptidase N (APN) as the primary entry port 61 (7). Surprisingly, its cousin HCoV-NL63 shares receptor specificity with the evolutionarily 62 distant SARS-CoV and SARS-CoV-2: all hijack angiotensin-converting enzyme 2 (ACE2) (8-63 11). HCoV-NL63 was also shown to use heparan sulfate as a primary attachment site (12-14). 64 A very different receptor is recognized by MERS-CoV, which binds to dipeptidyl-peptidase 4 65 (DPP4) (9, 15, 16). Another betacoronavirus, HCoV-OC43, binds to N-acetyl-9-O-66 acetylneuraminic acid (17, 18). HCoV-HKU1 remains the great unknown because its cellular 67 receptor has not been identified and all efforts to culture the virus in vitro have failed.68 HCoV-HKU1 was identified in Hong Kong in 2004. The virus was present in a sample 69 obtained from an elderly patient with severe pneumonia (...

show abstract

“…This abolished virus replication ex vivo , thereby confirming the importance of KLK13 during infection. KLK13 is thought to be secreted and membrane-bound( 82, 83 ).…”

Section: Discussionmentioning

confidence: 99%

Kallikrein 13: a new player in coronaviral infections

Milewska

Falkowski

Kalińska

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…We interpret this to mean that the residual mBDNF remaining is sufficient to allow for normal entrainment of the circadian clock by light. This residual BDNF is produced by the activation of plasmin by enzymes other than tPA, such as urokinase-type plasminogen activator [ 12 ] or other enzymes that perform this function such as kallikreins [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

Regulation of Locomotor activity in fed, fasted, and food-restricted mice lacking tissue-type plasminogen activator

et al. 2018

View full text Add to dashboard Cite

BackgroundCircadian rhythms of physiology and behavior are driven by a circadian clock located in the suprachiasmatic nucleus of the hypothalamus. This clock is synchronized to environmental day/night cycles by photic input, which is dependent on the presence of mature brain-derived neurotrophic factor (BDNF) in the SCN. Mature BDNF is produced by the enzyme plasmin, which is converted from plasminogen by the enzyme tissue-type plasminogen activator (tPA). In this study, we evaluate circadian function in mice lacking functional tPA.ResultstPA−/− mice have normal circadian periods, but show decreased nocturnal wheel-running activity. This difference is eliminated or reversed on the second day of a 48-h fast. Similarly, when placed on daily cycles of restricted food availability the genotypic difference in total wheel-running activity disappears, and tPA−/− mice show equivalent amounts of food anticipatory activity to wild type mice.ConclusionsThese data suggest that tPA regulates nocturnal wheel-running activity, and that tPA differentially affects SCN-driven nocturnal activity rhythms and activity driven by fasting or temporal food restriction.Electronic supplementary materialThe online version of this article (10.1186/s12899-018-0036-0) contains supplementary material, which is available to authorized users.

show abstract

“…The role of the plasminogen cascade enzymes in the epidermis has been discussed for 35 years . However, it was not until recently that their relevance in the SC was established .…”

Section: Discussionmentioning

confidence: 99%

“…Activation of pro‐uPA, the zymogen of uPA, generates catalytically active high molecular weight (HMW)‐uPA and a low molecular weight (LMW)‐uPA . A number of serine and cysteine proteases can activate pro‐uPA such as plasmin, matriptase, tryptase, and the various trypsin‐like KLKs and the cathepsins B and L . Outside of the circulation, plasminogen, the zymogen of plasmin, is mainly activated by uPA .…”

Section: Introductionmentioning

confidence: 99%