Origin of serpin-mediated regulation of coagulation and blood pressure

Wang Y, Köster K, Lummer M, Ragg H (2014)
PLoS ONE 9(5): e97879.

Zeitschriftenaufsatz | Veröffentlicht | Englisch
Abstract / Bemerkung
Vertebrates evolved an endothelium-lined hemostatic system and a pump-driven pressurized circulation with a finely-balanced coagulation cascade and elaborate blood pressure control over the past 500 million years. Genome analyses have identified principal components of the ancestral coagulation system, however, how this complex trait was originally regulated is largely unknown. Likewise, little is known about the roots of blood pressure control in vertebrates. Here we studied three members of the serpin superfamily that interfere with procoagulant activity and blood pressure of lampreys, a group of basal vertebrates. Angiotensinogen from these jawless fish was found to fulfill a dual role by operating as a highly selective thrombin inhibitor that is activated by heparin-related glycosaminoglycans, and concurrently by serving as source of effector peptides that activate type 1 angiotensin receptors. Lampreys, uniquely among vertebrates, thus use angiotensinogen for interference with both coagulation and osmo- and pressure regulation. Heparin cofactor II from lampreys, in contrast to its paralogue angiotensinogen, is preferentially activated by dermatan sulfate, suggesting that these two serpins affect different facets of thrombin’s multiple roles. Lampreys also express a lineage-specific serpin with anti-factor Xa activity, which demonstrates that another important procoagulant enzyme is under inhibitory control. Comparative genomics suggests that orthologues of these three serpins were key components of the ancestral hemostatic system. It appears that, early in vertebrate evolution, coagulation and osmo- and pressure regulation crosstalked through antiproteolytically active angiotensinogen, a feature that was lost during vertebrate radiation, though in gnathostomes interplay between these traits is effective.
Open-Access-Publikationskosten wurden durch die Deutsche Forschungsgemeinschaft und die Universität Bielefeld gefördert.
Page URI


Wang Y, Köster K, Lummer M, Ragg H. Origin of serpin-mediated regulation of coagulation and blood pressure. PLoS ONE. 2014;9(5): e97879.
Wang, Y., Köster, K., Lummer, M., & Ragg, H. (2014). Origin of serpin-mediated regulation of coagulation and blood pressure. PLoS ONE, 9(5), e97879. doi:10.1371/journal.pone.0097879
Wang, Yunjie, Köster, Katharina, Lummer, Martina, and Ragg, Hermann. 2014. “Origin of serpin-mediated regulation of coagulation and blood pressure”. PLoS ONE 9 (5): e97879.
Wang, Y., Köster, K., Lummer, M., and Ragg, H. (2014). Origin of serpin-mediated regulation of coagulation and blood pressure. PLoS ONE 9:e97879.
Wang, Y., et al., 2014. Origin of serpin-mediated regulation of coagulation and blood pressure. PLoS ONE, 9(5): e97879.
Y. Wang, et al., “Origin of serpin-mediated regulation of coagulation and blood pressure”, PLoS ONE, vol. 9, 2014, : e97879.
Wang, Y., Köster, K., Lummer, M., Ragg, H.: Origin of serpin-mediated regulation of coagulation and blood pressure. PLoS ONE. 9, : e97879 (2014).
Wang, Yunjie, Köster, Katharina, Lummer, Martina, and Ragg, Hermann. “Origin of serpin-mediated regulation of coagulation and blood pressure”. PLoS ONE 9.5 (2014): e97879.
Alle Dateien verfügbar unter der/den folgenden Lizenz(en):
Copyright Statement:
Dieses Objekt ist durch das Urheberrecht und/oder verwandte Schutzrechte geschützt. [...]
Access Level
OA Open Access
Zuletzt Hochgeladen
MD5 Prüfsumme

4 Zitationen in Europe PMC

Daten bereitgestellt von Europe PubMed Central.

How serpins transport hormones and regulate their release.
Carrell RW, Read RJ., Semin Cell Dev Biol 62(), 2017
PMID: 28027946
Heparin Binds Lamprey Angiotensinogen and Promotes Thrombin Inhibition through a Template Mechanism.
Wei H, Cai H, Wu J, Wei Z, Zhang F, Huang X, Ma L, Feng L, Zhang R, Wang Y, Ragg H, Zheng Y, Zhou A., J Biol Chem 291(48), 2016
PMID: 27681598

45 References

Daten bereitgestellt von Europe PubMed Central.

Palaeontology: modern look for ancient lamprey.
Janvier P., Nature 443(7114), 2006
PMID: 17066021
Sequencing of the sea lamprey (Petromyzon marinus) genome provides insights into vertebrate evolution.
Smith JJ, Kuraku S, Holt C, Sauka-Spengler T, Jiang N, Campbell MS, Yandell MD, Manousaki T, Meyer A, Bloom OE, Morgan JR, Buxbaum JD, Sachidanandam R, Sims C, Garruss AS, Cook M, Krumlauf R, Wiedemann LM, Sower SA, Decatur WA, Hall JA, Amemiya CT, Saha NR, Buckley KM, Rast JP, Das S, Hirano M, McCurley N, Guo P, Rohner N, Tabin CJ, Piccinelli P, Elgar G, Ruffier M, Aken BL, Searle SM, Muffato M, Pignatelli M, Herrero J, Jones M, Brown CT, Chung-Davidson YW, Nanlohy KG, Libants SV, Yeh CY, McCauley DW, Langeland JA, Pancer Z, Fritzsch B, de Jong PJ, Zhu B, Fulton LL, Theising B, Flicek P, Bronner ME, Warren WC, Clifton SW, Wilson RK, Li W., Nat. Genet. 45(4), 2013
PMID: 23435085
microRNAs reveal the interrelationships of hagfish, lampreys, and gnathostomes and the nature of the ancestral vertebrate.
Heimberg AM, Cowper-Sal-lari R, Semon M, Donoghue PC, Peterson KJ., Proc. Natl. Acad. Sci. U.S.A. 107(45), 2010
PMID: 20959416
Evolutionary origins of the blood vascular system and endothelium.
Monahan-Earley R, Dvorak AM, Aird WC., J. Thromb. Haemost. 11 Suppl 1(), 2013
PMID: 23809110
450 million years of hemostasis.
Davidson CJ, Tuddenham EG, McVey JH., J. Thromb. Haemost. 1(7), 2003
PMID: 12871284
Step-by-step evolution of vertebrate blood coagulation.
Doolittle RF., Cold Spring Harb. Symp. Quant. Biol. 74(), 2009
PMID: 19667012
Evolution of the contact phase of vertebrate blood coagulation. J Thromb Haemost 6: 1876–1883
Multiple gains of spliceosomal introns in a superfamily of vertebrate protease inhibitor genes.
Ragg H, Kumar A, Koster K, Bentele C, Wang Y, Frese MA, Prib N, Kruger O., BMC Evol. Biol. 9(), 2009
PMID: 19698129

Characterization of the protein Z-dependent protease inhibitor.
Han X, Fiehler R, Broze GJ Jr., Blood 96(9), 2000
PMID: 11049983
Heparin is a major activator of the anticoagulant serpin, protein Z-dependent protease inhibitor.
Huang X, Rezaie AR, Broze GJ Jr, Olson ST., J. Biol. Chem. 286(11), 2011
PMID: 21220417
An unexpected link between angiotensinogen and thrombin.
Wang Y, Ragg H., FEBS Lett. 585(14), 2011
PMID: 21722639
International union of pharmacology. XXIII. The angiotensin II receptors.
de Gasparo M, Catt KJ, Inagami T, Wright JW, Unger T., Pharmacol. Rev. 52(3), 2000
PMID: 10977869
Molecular analysis of the structure and function of the angiotensin II type 1 receptor.
Miura S, Saku K, Karnik SS., Hypertens. Res. 26(12), 2003
PMID: 14717335
Activation of heparin cofactor II by dermatan sulfate.
Tollefsen DM, Pestka CA, Monafo WJ., J. Biol. Chem. 258(11), 1983
PMID: 6687888
On the activation of human leuserpin-2, a thrombin inhibitor, by glycosaminoglycans.
Ragg H, Ulshofer T, Gerewitz J., J. Biol. Chem. 265(9), 1990
PMID: 2318889
Universal method facilitating the amplification of extremely GC-rich DNA fragments from genomic DNA.
Wei M, Deng J, Feng K, Yu B, Chen Y., Anal. Chem. 82(14), 2010
PMID: 20565067
Inhibition of furin by serpin Spn4A from Drosophila melanogaster.
Oley M, Letzel MC, Ragg H., FEBS Lett. 577(1-2), 2004
PMID: 15527779
A modular set of prokaryotic and eukaryotic expression vectors.
Melcher K., Anal. Biochem. 277(1), 2000
PMID: 10610695
Heparin-induced substrate behavior of antithrombin Cambridge II.
Mushunje A, Zhou A, Carrell RW, Huntington JA., Blood 102(12), 2003
PMID: 12907439
Ensembl 2013.
Flicek P, Ahmed I, Amode MR, Barrell D, Beal K, Brent S, Carvalho-Silva D, Clapham P, Coates G, Fairley S, Fitzgerald S, Gil L, Garcia-Giron C, Gordon L, Hourlier T, Hunt S, Juettemann T, Kahari AK, Keenan S, Komorowska M, Kulesha E, Longden I, Maurel T, McLaren WM, Muffato M, Nag R, Overduin B, Pignatelli M, Pritchard B, Pritchard E, Riat HS, Ritchie GR, Ruffier M, Schuster M, Sheppard D, Sobral D, Taylor K, Thormann A, Trevanion S, White S, Wilder SP, Aken BL, Birney E, Cunningham F, Dunham I, Harrow J, Herrero J, Hubbard TJ, Johnson N, Kinsella R, Parker A, Spudich G, Yates A, Zadissa A, Searle SM., Nucleic Acids Res. 41(Database issue), 2012
PMID: 23203987
MEGA5: molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods.
Tamura K, Peterson D, Peterson N, Stecher G, Nei M, Kumar S., Mol. Biol. Evol. 28(10), 2011
PMID: 21546353
Molecular determinants of angiotensin II type 1 receptor functional selectivity.
Aplin M, Bonde MM, Hansen JL., J. Mol. Cell. Cardiol. 46(1), 2008
PMID: 18848837
Role of Phe308 in the seventh transmembrane domain of the AT2 receptor in ligand binding and signaling.
Pulakat L, Mandavia CH, Gavini N., Biochem. Biophys. Res. Commun. 319(4), 2004
PMID: 15194486
Evolution by gene duplication: an update
Vertebrate serpins: construction of a conflict-free phylogeny by combining exon-intron and diagnostic site analyses.
Ragg H, Lokot T, Kamp PB, Atchley WR, Dress A., Mol. Biol. Evol. 18(4), 2001
PMID: 11264410
Thrombin inhibition by the serpins.
Huntington JA., J. Thromb. Haemost. 11 Suppl 1(), 2013
PMID: 23809129
Genomic evidence for a simpler clotting scheme in jawless vertebrates.
Doolittle RF, Jiang Y, Nand J., J. Mol. Evol. 66(2), 2008
PMID: 18283387
Semin Thromb Hemostas
Differential PI 3-kinase dependence of early and late phases of recycling of the internalized AT1 angiotensin receptor.
Hunyady L, Baukal AJ, Gaborik Z, Olivares-Reyes JA, Bor M, Szaszak M, Lodge R, Catt KJ, Balla T., J. Cell Biol. 157(7), 2002
PMID: 12070129
Angiotensin II revisited: new roles in inflammation, immunology and aging.
Benigni A, Cassis P, Remuzzi G., EMBO Mol Med 2(7), 2010
PMID: 20597104
The angiotensin system elements in invertebrates.
Salzet M, Deloffre L, Breton C, Vieau D, Schoofs L., Brain Res. Brain Res. Rev. 36(1), 2001
PMID: 11516771
Screening mammal biodiversity using DNA from leeches.
Schnell IB, Thomsen PF, Wilkinson N, Rasmussen M, Jensen LR, Willerslev E, Bertelsen MF, Gilbert MT., Curr. Biol. 22(8), 2012
PMID: 22537625
Thrombin as a multi-functional enzyme. Focus on in vitro and in vivo effects.
Siller-Matula JM, Schwameis M, Blann A, Mannhalter C, Jilma B., Thromb. Haemost. 106(6), 2011
PMID: 21979864
The roles of proteinase-activated receptors in the vascular physiology and pathophysiology.
Hirano K., Arterioscler. Thromb. Vasc. Biol. 27(1), 2006
PMID: 17095716
Is thrombin a key player in the 'coagulation-atherogenesis' maze?
Borissoff JI, Spronk HM, Heeneman S, ten Cate H., Cardiovasc. Res. 82(3), 2009
PMID: 19228706
Heparin cofactor II, a serine protease inhibitor, promotes angiogenesis via activation of the AMP-activated protein kinase-endothelial nitric-oxide synthase signaling pathway.
Ikeda Y, Aihara K, Yoshida S, Iwase T, Tajima S, Izawa-Ishizawa Y, Kihira Y, Ishizawa K, Tomita S, Tsuchiya K, Sata M, Akaike M, Kato S, Matsumoto T, Tamaki T., J. Biol. Chem. 287(41), 2012
PMID: 22904320

Markieren/ Markierung löschen
Markierte Publikationen

Open Data PUB

Web of Science

Dieser Datensatz im Web of Science®

PMID: 24840053
PubMed | Europe PMC

Suchen in

Google Scholar