Claus Oxvig's Publications List

Severe preeclampsia-related changes in gene expression at the maternal-fetal interface include sialic acid-binding immunoglobulin-like lectin-6 and pappalysin-2.

2009-05-26T14:33:36Z

Preeclampsia (PE), which affects 4-8% of human pregnancies, causes significant maternal and neonatal morbidity and mortality. Within the basal plate, placental cytotrophoblasts (CTBs) of fetal origin invade the uterus and extensively remodel the maternal vasculature. In PE, CTB invasion is often shallow, and vascular remodeling is rudimentary. To better understand possible causes, we conducted a g...

Virginia D Winn, Matthew Gormley, Agnes C Paquet, Kasper Kjaer-Sorensen, Anita Kramer, Kristen K Rumer, Ronit Haimov-Kochman, Ru-Fang Yeh, Michael T Overgaard, Ajit Varki, Claus Oxvig, Susan J Fisher (2009) Endocrinology 150: 1 452-462

Temporal course of pregnancy-associated plasma protein-A in angioplasty-treated ST-elevation myocardial infarction patients and potential significance of concomitant heparin administration.

2009-05-26T14:33:36Z

Pregnancy-associated plasma protein-A (PAPP-A) is a putative plaque instability marker. In acute coronary syndromes, the disrupted culprit plaque contains abundant PAPP-A, and circulating PAPP-A levels predict clinical outcomes. Determinants of circulating PAPP-A levels, however, are not fully understood, and the potential role of concomitant heparin administration has not previously been evaluate...

Christian J Terkelsen, Claus Oxvig, Bjarne L Nørgaard, Simon Glerup, Tina S Poulsen, Jens F Lassen, Holger J Møller, Leif Thuesen, Erling Falk, Torsten T Nielsen, Henning R Andersen (2009) Am J Cardiol 103: 1 29-35

LRP1 controls biosynthetic and endocytic trafficking of neuronal prion protein.

2009-05-26T14:33:36Z

The trafficking of normal cellular prion protein (PrPC) is believed to control its conversion to the altered conformation (designated PrPSc) associated with prion disease. Although anchored to the membrane by means of glycosylphosphatidylinositol (GPI), PrPC on neurons is rapidly and constitutively endocytosed by means of coated pits, a property dependent upon basic amino acids at its N-terminus. ...

Celia J Parkyn, Esmeralda G M Vermeulen, Roy C Mootoosamy, Claire Sunyach, Christian Jacobsen, Claus Oxvig, Søren Moestrup, Qiang Liu, Guojun Bu, Angela Jen, Roger J Morris (2008) J Cell Sci 121: Pt 6 773-783

Inhibition of the proteolytic activity of pregnancy-associated plasma protein-A by targeting substrate exosite binding.

2009-05-26T14:33:36Z

The metalloproteinase pregnancy-associated plasma protein-A (PAPP-A) cleaves both insulin-like growth factor (IGF)-binding protein 4 (IGFBP-4) and -5 at a single site in their central domain causing the release of bioactive IGF. Inhibition of IGF signaling is relevant in human disease, and several drugs in development target the IGF receptor. However, inhibition of PAPP-A activity may be a valuabl...

Jakob H Mikkelsen, Claus Gyrup, Peter Kristensen, Michael T Overgaard, Christine B Poulsen, Lisbeth S Laursen, Claus Oxvig (2008) J Biol Chem 283: 24 16772-16780

Duplication and diversification of the hypoxia-inducible IGFBP-1 gene in zebrafish.

2009-05-26T14:33:36Z

BACKGROUND: Gene duplication is the primary force of new gene evolution. Deciphering whether a pair of duplicated genes has evolved divergent functions is often challenging. The zebrafish is uniquely positioned to provide insight into the process of functional gene evolution due to its amenability to genetic and experimental manipulation and because it possess a large number of duplicated genes. M...

Hiroyasu Kamei, Ling Lu, Shuang Jiao, Yun Li, Claus Gyrup, Lisbeth S Laursen, Claus Oxvig, Jianfeng Zhou, Cunming Duan (2008) PLoS ONE 3: 8

Quantitative analysis of insulin-like growth factor-modulated proteolysis of insulin-like growth factor binding protein-4 and -5 by pregnancy-associated plasma protein-A.

2009-05-26T14:33:36Z

The metzincin metalloproteinase pregnancy-associated plasma protein-A (PAPP-A, pappalysin-1, EC 3.4.24.79) specifically cleaves insulin-like growth factor binding protein (IGFBP)-4 and -5. Regulation of insulin-like growth factor (IGF) bioavailability through cleavage of these inhibitory binding proteins is an important mechanism for the control of growth and development of vertebrate cells. Altho...

Claus Gyrup, Claus Oxvig (2007) Biochemistry 46: 7 1972-1980

Cell surface detachment of pregnancy-associated plasma protein-A requires the formation of intermolecular proteinase-inhibitor disulfide bonds and glycosaminoglycan covalently bound to the inhibitor.

2009-05-26T14:33:36Z

The metzincin metalloproteinase pregnancy-associated plasma protein-A (PAPP-A, pappalysin-1) promotes cell growth by proteolytic cleavage of insulin-like growth factor-binding proteins 4 and 5, causing the release of bound insulin-like growth factors. PAPP-A binds an unknown cell-surface heparan sulfate proteoglycan, suggesting that it controls insulin-like growth factor signaling spatially. In hu...

Simon Glerup, Søren Kløverpris, Lisbeth S Laursen, Frederik Dagnaes-Hansen, Steffen Thiel, Cheryl A Conover, Claus Oxvig (2007) J Biol Chem 282: 3 1769-1778

Surface association of pregnancy-associated plasma protein-A accounts for its colocalization with activated macrophages.

2009-05-26T14:33:36Z

Intense immunostaining for pregnancy-associated plasma protein-A (PAPP-A), a newly characterized metalloproteinase in the insulin-like growth factor system, colocalizes with activated macrophages in human atherosclerotic plaque. To determine macrophage regulation of PAPP-A expression, we developed two models of human macrophages with basal and activated phenotypes. THP-1 cells and peripheral blood...

Cheryl A Conover, Sean C Harrington, Laurie K Bale, Claus Oxvig (2007) Am J Physiol Heart Circ Physiol 292: 2 H994-H1000

Regulation of insulin-like growth factor (IGF) bioactivity by sequential proteolytic cleavage of IGF binding protein-4 and -5.

2009-05-26T14:33:36Z

The biological activity of IGF-I and -II is controlled by six binding proteins (IGFBPs), preventing the IGFs from interacting with the IGF receptor. Proteolytic cleavage of IGFBPs is one mechanism by which IGF can be released to bind the receptor. The IGFBPs are usually studied individually, although the presence of more than one of the IGFBPs in most tissues suggests a cooperative function. Thus,...

Lisbeth S Laursen, Kasper Kjaer-Sorensen, Mikkel H Andersen, Claus Oxvig (2007) Mol Endocrinol 21: 5 1246-1257

Quantification of proteolytically active pregnancy-associated plasma protein-A with an assay based on quenched fluorescence.

2009-05-26T14:33:36Z

BACKGROUND: Maternal serum concentrations of pregnancy-associated plasma protein-A (PAPP-A, pappalysin-1, EC 3.4.24.79) are used to predict the occurrence of Down syndrome. In pregnancy, PAPP-A primarily circulates as a covalent 2:2 complex with the proform of eosinophil major basic protein (proMBP), which inhibits the proteolytic activity of PAPP-A. At term, however, approximately 1% of PAPP-A ex...

Claus Gyrup, Michael Christiansen, Claus Oxvig (2007) Clin Chem 53: 5 947-954

The structural basis of calcium transport by the calcium pump.

2009-05-26T14:33:36Z

The sarcoplasmic reticulum Ca2+-ATPase, a P-type ATPase, has a critical role in muscle function and metabolism. Here we present functional studies and three new crystal structures of the rabbit skeletal muscle Ca2+-ATPase, representing the phosphoenzyme intermediates associated with Ca2+ binding, Ca2+ translocation and dephosphorylation, that are based on complexes with a functional ATP analogue, ...

Claus Olesen, Martin Picard, Anne-Marie Lund Winther, Claus Gyrup, J Preben Morth, Claus Oxvig, Jesper Vuust Møller, Poul Nissen (2007) Nature 450: 7172 1036-1042

A substrate specificity-determining unit of three Lin12-Notch repeat modules is formed in trans within the pappalysin-1 dimer and requires a sequence stretch C-terminal to the third module.

2009-05-26T14:33:36Z

Members of the pappalysin family of metzincin metalloproteinases, pregnancy-associated plasma protein-A (PAPP-A, pappalysin-1) and PAPP-A2 (pappalysin-2), regulate the bioavailability of insulin-like growth factors (IGFs) by specific proteolytic inactivation of IGF-binding proteins (IGFBPs). PAPP-A cleaves IGFBP-4 and IGFBP-5, whereas PAPP-A2 cleaves only IGFBP-5. The pappalysins contain three Lin...

Kathrin Weyer, Henning B Boldt, Christine B Poulsen, Kasper Kjaer-Sorensen, Claus Gyrup, Claus Oxvig (2007) J Biol Chem 282: 15 10988-10999

Prognostic value of circulating pregnancy-associated plasma protein levels in patients with chronic stable angina.

2009-05-26T14:33:36Z

AIMS: Unstable coronary atherosclerotic plaque can be present in patients with chronic stable coronary artery disease (CAD). Our objective was to assess whether measurement of plasma pregnancy-associated plasma protein (PAPP-A) level, a reflection of plaque instability, in patients with chronic stable CAD had an independent prognostic value on the subsequent incidence of death, acute coronary synd...

Ahmad A Elesber, Cheryl A Conover, Ali E Denktas, Ryan J Lennon, David R Holmes, Michael T Overgaard, Michael Christiansen, Claus Oxvig, Lilach O Lerman, Amir Lerman (2006) Eur Heart J 27: 14 1678-1684

Cytokine stimulation of pregnancy-associated plasma protein A expression in human coronary artery smooth muscle cells: inhibition by resveratrol.

2009-05-26T14:33:36Z

Through specific cleavage of proteins that bind and inhibit insulin-like growth factor-I (IGF-I), pregnancy-associated plasma protein-A (PAPP-A) enhances local IGF-I availability, and, consequently, receptor activation. PAPP-A expression is increased in experimental models of vascular injury and in human atherosclerotic plaque; however, little is known about the regulation of PAPP-A gene expressio...

Cheryl A Conover, Laurie K Bale, Sean C Harrington, Zachary T Resch, Michael T Overgaard, Claus Oxvig (2006) Am J Physiol Cell Physiol 290: 1 C183-C188

Stress-activated signaling pathways mediate the stimulation of pregnancy-associated plasma protein-A expression in cultured human fibroblasts.

2009-05-26T14:33:36Z

Pregnancy-associated plasma protein-A (PAPP-A) is an IGF binding protein protease that appears to function as a posttranslational modulator of IGF bioavailability in response to injury. A previous study indicated that the proinflammatory cytokines, TNFalpha and IL-1beta, were potent stimulators of PAPP-A expression in cultured human fibroblasts. In this study, we investigated the intracellular sig...

Zachary T Resch, Claus Oxvig, Laurie K Bale, Cheryl A Conover (2006) Endocrinology 147: 2 885-890

Pregnancy-associated plasma protein-a is markedly expressed by monocyte-macrophage cells in vulnerable and ruptured carotid atherosclerotic plaques: a link between inflammation and cerebrovascular events.

2009-05-26T14:33:36Z

OBJECTIVES: The study aim was to evaluate serologic expression of pregnancy-associated protein-A (PAPP-A) in patients affected by cerebrovascular accidents and to correlate it with histopathologic carotid plaque complexity. BACKGROUND: Little is known about PAPP-A expression in carotid atherosclerotic disease and whether this protein represents a marker of plaque vulnerability also in carotid dist...

Giuseppe Sangiorgi, Alessandro Mauriello, Elena Bonanno, Claus Oxvig, Cheryl A Conover, Michael Christiansen, Santi Trimarchi, Vincenzo Rampoldi, David R Holmes, Robert S Schwartz, Luigi Giusto Spagnoli (2006) J Am Coll Cardiol 47: 11 2201-2211

Definition, expression, and characterization of a protein domain in the N-terminus of pregnancy-associated plasma protein-A distantly related to the family of laminin G-like modules.

2009-05-26T14:33:36Z

Although pregnancy-associated plasma protein-A (PAPP-A), a modulator of insulin-like growth factor (IGF) activity through its cleavage of IGF-binding protein (IGFBP)-4 and -5, has been known for more than two decades, knowledge about its domain architecture is still incomplete. Using position-specific iterative BLAST, we have identified distant relatives of the PAPP-A N-terminal sequence stretch o...

Henning B Boldt, Simon Glerup, Michael T Overgaard, Lars Sottrup-Jensen, Claus Oxvig (2006) Protein Expr Purif 48: 2 261-273

The GH-IGF-IGFBP axis is changed in Turner syndrome: partial normalization by HRT.

2009-05-26T14:33:36Z

BACKGROUND: We recently described increased insulin-like growth factor binding protein 3 (IGFBP-3) proteolysis in the circulation in adult Turner syndrome (TS), with normalization during sex hormone replacement therapy (HRT), suggesting the presence of a sex hormone regulated IGFBP-3 proteolytic activity. OBJECTIVE: To study the GH-IGF-IGFBP axis in TS without and during HRT, and to further charac...

Claus Højbjerg Gravholt, Jian-Wen Chen, Claus Oxvig, Michael T Overgaard, Jens Sandahl Christiansen, Jan Frystyk, Allan Flyvbjerg (2006) Growth Horm IGF Res 16: 5-6 332-339

The proform of the eosinophil major basic protein binds the cell surface through a site distinct from its C-type lectin ligand-binding region.

2009-05-26T14:33:36Z

The highly basic eosinophil major basic protein (MBP), present in the crystalloid core of eosinophil leukocyte granules, has both cytotoxic and cytostimulatory properties and is directly implicated in a number of diseases. The crystal structure of MBP resembles that of the C-type lectin (CTL) superfamily, and recent data showed that MBP binds heparan sulfate glycosaminoglycan (GAG), with the CTL l...

Simon Glerup, Søren Kløverpris, Claus Oxvig (2006) J Biol Chem 281: 42 31509-31516

Haptoglobin-related protein is a high-affinity hemoglobin-binding plasma protein.

2009-05-26T14:33:36Z

Haptoglobin-related protein (Hpr) is a primate-specific plasma protein associated with apolipoprotein L-I (apoL-I)-containing high-density lipoprotein (HDL) particles shown to be a part of the innate immune defense. Despite the assumption hitherto that Hpr does not bind to hemoglobin, the present study revealed that recombinant Hpr binds hemoglobin as efficiently as haptoglobin (Hp). However, in c...

Marianne Jensby Nielsen, Steen Vang Petersen, Christian Jacobsen, Claus Oxvig, David Rees, Holger Jon Møller, Søren Kragh Moestrup (2006) Blood 108: 8 2846-2849

Proteinase inhibition by proform of eosinophil major basic protein (pro-MBP) is a multistep process of intra- and intermolecular disulfide rearrangements.

2009-05-26T14:33:36Z

The metzincin metalloproteinase pregnancy-associated plasma protein A (PAPP-A, pappalysin-1) promotes cell growth by the cleavage of insulin-like growth factor-binding proteins-4 and -5, causing the release of bound insulin-like growth factors. The proteolytic activity of PAPP-A is inhibited by the proform of eosinophil major basic protein (pro-MBP), which forms a covalent 2:2 proteinase-inhibitor...

Simon Glerup, Henning B Boldt, Michael T Overgaard, Lars Sottrup-Jensen, Linda C Giudice, Claus Oxvig (2005) J Biol Chem 280: 11 9823-9832

Real-time measurement in living cells of insulin-like growth factor activity using bioluminescence resonance energy transfer.

2009-05-26T14:33:36Z

Insulin-like growth factor (IGF)-I and -II function in normal physiology to control growth, development, and differentiation, but are also important in pathophysiological conditions, particularly in cancer. The biological effects of the IGFs are mediated by the IGF-I receptor (IGFR), a covalent homodimer composed of two alpha and two beta chains, similar in structure to the insulin receptor (IR). ...

Lisbeth S Laursen, Claus Oxvig (2005) Biochem Pharmacol 69: 12 1723-1732

Relationship among pregnancy associated plasma protein-A levels, clinical characteristics, and coronary artery disease extent in patients with chronic stable angina pectoris.

2009-05-26T14:33:36Z

AIMS: To assess, in chronic stable angina (CSA) patients, the relationship among clinical characteristics and cardiovascular risk factors, extent of coronary artery disease (CAD), and pregnancy-associated plasma protein-A (PAPP-A) levels. METHODS AND RESULTS: We studied 643 CSA patients (63+/-10 years, 482 men) undergoing diagnostic coronary angiography; 97 with angiographically normal coronary ar...

Juan Cosin-Sales, Juan Carlos Kaski, Michael Christiansen, Paul Kaminski, Claus Oxvig, Michael T Overgaard, Della Cole, David W Holt (2005) Eur Heart J 26: 20 2093-2098

Pregnancy-associated plasma protein a gene expression as a target of inflammatory cytokines.

2009-05-26T14:33:36Z

Pregnancy-associated plasma protein A (PAPP-A) cleaves IGF-binding protein-4 (IGFBP-4) and appears to enhance local IGF bioavailability in response to injury. In this study we determined the effects of growth factors and cytokines involved in the healing process on PAPP-A expression in human dermal fibroblasts. There was no effect of platelet-derived growth factor, epidermal growth factor, or basi...

Zachary T Resch, Bing-Kun Chen, Laurie K Bale, Claus Oxvig, Michael T Overgaard, Cheryl A Conover (2004) Endocrinology 145: 3 1124-1129

Pregnancy-associated plasma protein A and its endogenous inhibitor, the proform of eosinophil major basic protein (proMBP), are related to complex stenosis morphology in patients with stable angina pectoris.

2009-05-26T14:33:36Z

BACKGROUND: The metalloproteinase pregnancy-associated plasma protein-A (PAPP-A) has been implicated in coronary plaque disruption. Its endogenous inhibitor, the proform of eosinophil major basic protein (proMBP), may also play a role in this process. Atheromatous plaque disruption often presents as complex angiographic lesions. We sought to assess whether PAPP-A, proMBP, and PAPP-A/ProMBP ratio a...

Juan Cosin-Sales, Michael Christiansen, Paul Kaminski, Claus Oxvig, Michael T Overgaard, Della Cole, David W Holt, Juan Carlos Kaski (2004) Circulation 109: 14 1724-1728

Metalloproteinase pregnancy-associated plasma protein A is a critical growth regulatory factor during fetal development.

2009-05-26T14:33:36Z

Pregnancy-associated plasma protein A (PAPPA) is a metzincin superfamily metalloproteinase in the insulin-like growth factor (IGF) system. PAPPA increases IGF bioavailability and mitogenic effectiveness in vitro through regulated cleavage of IGF-binding protein 4 (IGFBP4). To determine its function in vivo, we generated PAPPA-null mice by gene targeting. Mice homozygous for targeted disruption of ...

Cheryl A Conover, Laurie K Bale, Michael T Overgaard, Edward W Johnstone, Ulla H Laursen, Ernst-Martin Füchtbauer, Claus Oxvig, Jan van Deursen (2004) Development 131: 5 1187-1194

Screening for Down's syndrome in early and late first and second trimester using six maternal serum markers.

2009-05-26T14:33:36Z

The efficiency of six maternal serum markers for Down's syndrome (DS), alpha fetoprotein (AFP), human chorionic gonadotropin (hCG), free beta-hCG, pregnancy-associated plasma protein-A (PAPP-A), the proform of eosinophil major basic protein (ProMBP), pregnancy-specific-beta-1-glycoprotein (SP(1)), and combinations thereof, was examined. Discriminant analysis in 156 DS pregnancies and 546 controls ...

M Christiansen, S O Larsen, C Oxvig, Q-P Qin, J M Wagner, M T Overgaard, G J Gleich, L Sottrup-Jensen, B Nørgaard-Pedersen (2004) Clin Genet 65: 1 11-16

Inhibition of proteolysis by the proform of eosinophil major basic protein (proMBP) requires covalent binding to its target proteinase.

2009-05-26T14:33:36Z

By proteolytic cleavage of insulin-like growth factor binding proteins, the metalloproteinase pregnancy-associated plasma protein-A (PAPP-A) is able to control the biological activity of insulin-like growth factors. PAPP-A circulates in pregnancy as a proteolytically inactive complex, disulfide bound to the proform of eosinophil major basic protein (proMBP). We here demonstrate that co-transfectio...

Michael T Overgaard, Simon Glerup, Henning B Boldt, Vivien Rodacker, Inger M Olsen, Michael Christiansen, Lars Sottrup-Jensen, Linda C Giudice, Claus Oxvig (2004) FEBS Lett 560: 1-3 147-152

Pregnancy-associated plasma protein-A (PAPP-A) expression and insulin-like growth factor binding protein-4 protease activity in normal and malignant ovarian surface epithelial cells.

2009-05-26T14:33:36Z

Pregnancy-Associated Plasma Protein-A (PAPP-A) proteolyses insulin-like growth factor binding protein-4 (IGFBP-4), thereby regulating local IGF availability. Reduced PAPP-A mRNA expression has been reported in ovarian cancer specimens compared to normal ovarian surface epithelial cells (OSE). To characterize PAPP-A expression and proteolytic activity in OSE, we developed a lifespan-extended human ...

Kimberly R Kalli, Bing-Kun Chen, Laurie K Bale, Erica Gernand, Michael T Overgaard, Claus Oxvig, William A Cliby, Cheryl A Conover (2004) Int J Cancer 110: 5 633-640

Cell surface adhesion of pregnancy-associated plasma protein-A is mediated by four clusters of basic residues located in its third and fourth CCP module.

2009-05-26T14:33:36Z

The metalloproteinase pregnancy-associated plasma protein-A (PAPP-A) cleaves a subset of insulin-like growth factor binding proteins (IGFBP), which inhibit the activities of insulin-like growth factor (IGF). Through this proteolytic activity, PAPP-A is believed to regulate IGF bioavailability in several biological systems, including the human reproductive system and the cardiovascular system. PAPP...

Kathrin Weyer, Michael T Overgaard, Lisbeth S Laursen, Claus G Nielsen, Alexander Schmitz, Michael Christiansen, Lars Sottrup-Jensen, Linda C Giudice, Claus Oxvig (2004) Eur J Biochem 271: 8 1525-1535

IGFBP-4 degradation by pregnancy-associated plasma protein-A in MC3T3 osteoblasts.

2009-05-26T14:33:36Z

Insulin-like growth factor (IGF) signaling is critical for osteoblast development and IGF binding protein (IGFBP)-4 is one of the principle IGFBPs expressed by osteoblasts. Release of bound IGF via proteolytic degradation of IGFBP-4 is likely to be critical for osteoblast development. We have investigated whether IGF-sensitive, IGFBP-4 degradation in mouse MC3T3-E1 osteoblasts is due to the metzin...

R Clay Bunn, Latonya D Green, Michael T Overgaard, Claus Oxvig, John L Fowlkes (2004) Biochem Biophys Res Commun 325: 3 698-706

Proteolytic degradation of IGF-binding protein (IGFBP)-2 in equine ovarian follicles: involvement of pregnancy-associated plasma protein-A (PAPP-A) and association with dominant but not subordinated follicles.

2009-05-26T14:33:36Z

In the ovary of mammalian species, terminal follicular growth is accompanied by a decrease in intrafollicular levels of IGF-binding protein-2 (IGFBP-2) and IGFBP-4. The decrease in IGFBP-4 levels is essentially due to an increase in proteolytic cleavage by intrafollicular pregnancy-associated plasma protein-A (PAPP-A) in growing healthy follicles. The decrease in IGFBP-2 levels is partly due to a ...

N Gérard, T Delpuech, C Oxvig, M T Overgaard, P Monget (2004) J Endocrinol 182: 3 457-466

The Lin12-notch repeats of pregnancy-associated plasma protein-A bind calcium and determine its proteolytic specificity.

2009-05-26T14:33:36Z

The Lin12-Notch repeat (LNR) module of about 35 residues is a hallmark of the Notch receptor family. Three copies, arranged in tandem, are invariably present in the extracellular portion of the Notch receptors. Although their function is unknown, genetic and biochemical data indicate that the LNR modules participate in the regulation of ligand-induced proteolytic cleavage of the Notch receptor, a ...

Henning B Boldt, Kasper Kjaer-Sorensen, Michael T Overgaard, Kathrin Weyer, Christine B Poulsen, Lars Sottrup-Jensen, Cheryl A Conover, Linda C Giudice, Claus Oxvig (2004) J Biol Chem 279: 37 38525-38531

Transforming growth factor-beta regulation of the insulin-like growth factor binding protein-4 protease system in cultured human osteoblasts.

2009-05-26T14:33:36Z

IGFBP-4 is an inhibitor of IGF-I in bone. We show that TGF-beta regulates IGFBP-4 and enhances IGF-I-stimulated growth of cultured human bone cells through increased expression of an IGFBP-4 protease, PAPP-A. This effect of TGF-beta on IGF-I bioavailability may promote local bone formation. Insulin-like growth factor binding protein (IGFBP-4) proteolysis is implicated in the regulation of local in...

Christopher O Ortiz, Bing-Kun Chen, Laurie K Bale, Michael T Overgaard, Claus Oxvig, Cheryl A Conover (2003) J Bone Miner Res 18: 6 1066-1072

Unstable carotid plaque: biochemical and cellular marker of vulnerability

2009-05-26T14:33:36Z

Stroke is the second most common cause of death in developed countries. Carotid plaque disruption and distal embolization of atheromatous debris are the most common pathogenic mechanisms for cerebral ischemia from carotid atherosclerotic disease. Morphologic composition of the atherosclerotic plaque, rather than the stenotic severity, appears to be central in determining the risk of both plaque ru...

Giannignazio Luigi Carbone, Alessandro Mauriello, Michael Christiansen, Claus Oxvig, Luigi Giusto Spagnoli, Robert S Schwartz, Giuseppe Sangiorgi (2003) Ital Heart J Suppl 4: 5 398-406

Pregnancy-associated plasma protein-A is involved in insulin-like growth factor binding protein-2 (IGFBP-2) proteolytic degradation in bovine and porcine preovulatory follicles: identification of cleavage site and characterization of IGFBP-2 degradation.

2009-05-26T14:33:36Z

In mammalian ovaries, terminal follicular growth is accompanied by a decrease in levels of intrafollicular insulin-like growth factor binding protein-2 (IGFBP-2) and IGFBP-4. The decrease in IGFBP-4 is essentially due to an increase in proteolytic degradation by intrafollicular pregnancy-associated plasma protein-A (PAPP-A) in growing healthy follicles. In contrast, the decrease in IGFBP-2 is part...

Philippe Monget, Sabine Mazerbourg, Thierry Delpuech, Marie-Christine Maurel, Sébastien Manière, Jürgen Zapf, Gilles Lalmanach, Claus Oxvig, Michael T Overgaard (2003) Biol Reprod 68: 1 77-86

Localization and regulation of pregnancy-associated plasma protein a expression in healing human skin.

2009-05-26T14:33:36Z

Pregnancy-associated plasma protein A (PAPP-A) is an IGF-binding protein-4 (IGFBP-4) metalloproteinase that cleaves inhibitory IGFBP-4 to amplify local IGF-I bioavailability in vitro. Thus it has functional implications in injury/repair responses. In this study we determined PAPP-A expression in healing human skin. Wounds were induced with a scalpel on the forearms of three normal subjects and wer...

Bing-Kun Chen, Kristin M Leiferman, Mark R Pittelkow, Michael T Overgaard, Claus Oxvig, Cheryl A Conover (2003) J Clin Endocrinol Metab 88: 9 4465-4471

Plasma C3d levels of young farmers correlate with respirable dust exposure levels during normal work in swine confinement buildings.

2009-05-26T14:33:36Z

Work in swine confinement buildings leads to an inflammatory response and may be associated with increased levels of acute phase proteins. We compared the inflammatory response of a control group of young former farm workers with age-matched former farm workers who had previously developed the lower airway symptoms of wheeze, cough, tightness of the chest during work in swine confinement buildings...

Hans Jürgen Hoffmann, Martin Iversen, Ivan Brandslund, Torben Sigsgaard, Øyvind Omland, Claus Oxvig, Uffe Holmskov, Leif Bjermer, Jens Christian Jensenius, Ronald Dahl (2003) Ann Agric Environ Med 10: 1 53-60

Complex of pregnancy-associated plasma protein-A and the proform of eosinophil major basic protein. Disulfide structure and carbohydrate attachment.

2009-05-26T14:33:36Z

Pregnancy-associated plasma protein-A (PAPP-A) is a metzincin superfamily metalloproteinase responsible for cleavage of insulin-like growth factor-binding protein-4, thus causing release of bound insulin-like growth factor. PAPP-A is secreted as a dimer of 400 kDa but circulates in pregnancy as a disulfide-bound 500-kDa 2:2 complex with the proform of eosinophil major basic protein (pro-MBP), rece...

Michael T Overgaard, Esben S Sorensen, Damian Stachowiak, Henning B Boldt, Lene Kristensen, Lars Sottrup-Jensen, Claus Oxvig (2003) J Biol Chem 278: 4 2106-2117

Expression of recombinant murine pregnancy-associated plasma protein-A (PAPP-A) and a novel variant (PAPP-Ai) with differential proteolytic activity.

2009-05-26T14:33:36Z

Murine pregnancy-associated plasma protein-A (PAPP-A) cDNA encoding a 1545 amino-acid protein has been cloned. We have also identified and cloned cDNA that encodes a novel variant of PAPP-A, PAPP-Ai, carrying a 29-residue highly basic insert. The point of insertion corresponds to a junction between two exons in the human PAPP-A gene. The human intron flanked by these exons does not encode a homolo...

Rikke Søe, Michael T Overgaard, Anni R Thomsen, Lisbeth S Laursen, Inger M Olsen, Lars Sottrup-Jensen, Jesper Haaning, Linda C Giudice, Cheryl A Conover, Claus Oxvig (2002) Eur J Biochem 269: 8 2247-2256

Molecular regulation of the IGF-binding protein-4 protease system in human fibroblasts: identification of a novel inducible inhibitor.

2009-05-26T14:33:36Z

The IGF-binding protein-4 (IGFBP-4) protease system is an important regulator of local IGF bioavailability and cell growth. Recently, the IGF-dependent IGFBP-4 protease secreted by cultured human fibroblasts was identified as pregnancy-associated plasma protein A (PAPP-A). In pregnancy serum, PAPP-A circulates as a disulfide-bound complex with the precursor form of major basic protein (pro-MBP), a...

Bing-Kun Chen, Michael T Overgaard, Laurie K Bale, Zachary T Resch, Michael Christiansen, Claus Oxvig, Cheryl A Conover (2002) Endocrinology 143: 4 1199-1205

Substrate specificity of the metalloproteinase pregnancy-associated plasma protein-A (PAPP-A) assessed by mutagenesis and analysis of synthetic peptides: substrate residues distant from the scissile bond are critical for proteolysis.

2009-05-26T14:33:36Z

Human pregnancy-associated plasma protein-A (PAPP-A) cleaves insulin-like growth factor (IGF) binding protein-4 (IGFBP-4), causing a dramatic reduction in its affinity for IGF-I and -II. Through this mechanism, PAPP-A is a regulator of IGF bioactivity in several systems, including the human ovary and the cardiovascular system. PAPP-A belongs to the metzincin superfamily of zinc metalloproteinases,...

Lisbeth S Laursen, Michael T Overgaard, Claus G Nielsen, Henning B Boldt, Kathrin H Hopmann, Cheryl A Conover, Lars Sottrup-Jensen, Linda C Giudice, Claus Oxvig (2002) Biochem J 367: Pt 1 31-40

Identification and regulation of the IGFBP-4 protease and its physiological inhibitor in human trophoblasts and endometrial stroma: evidence for paracrine regulation of IGF-II bioavailability in the placental bed during human implantation.

2009-05-26T14:33:36Z

The IGF family plays an important role in implantation and placental physiology. IGF-II is abundantly expressed by placental trophoblasts, and IGF binding protein (IGFBP)-4, a potent inhibitor of IGF actions, is the second most abundant IGFBP in the placental bed, expressed exclusively by the maternal decidua. Proteolysis of IGFBP-4 results in decreased affinity for IGF peptides, thereby enhancing...

L C Giudice, C A Conover, L Bale, G H Faessen, K Ilg, I Sun, B Imani, L-F Suen, J C Irwin, M Christiansen, M T Overgaard, C Oxvig (2002) J Clin Endocrinol Metab 87: 5 2359-2366

Cell surface targeting of pregnancy-associated plasma protein A proteolytic activity. Reversible adhesion is mediated by two neighboring short consensus repeats.

2009-05-26T14:33:36Z

The activities of insulin-like growth factor (IGF)-I and -II are regulated by IGF-binding proteins (IGFBPs). Cleavage of IGFBP-4 by the metalloproteinase pregnancy-associated plasma protein-A (PAPP-A) causes release of bound IGF and has been established in several biological systems including the human reproductive system. Using flow cytometry, we first demonstrate that PAPP-A reversibly binds to ...

Lisbeth S Laursen, Michael T Overgaard, Kathrin Weyer, Henning B Boldt, Peter Ebbesen, Michael Christiansen, Lars Sottrup-Jensen, Linda C Giudice, Claus Oxvig (2002) J Biol Chem 277: 49 47225-47234

Pregnancy-associated plasma protein A proteolytic activity is associated with the human placental trophoblast cell membrane.

2009-05-26T14:33:36Z

Pregnancy-associated plasma protein-A (PAPP-A) is a product of the placenta and decidua and is secreted into the maternal circulation during human pregnancy. It recently has been identified as an IGF binding protein (IGFBP)-4 protease. Presumed functions at the maternal-fetal interface are to proteolyze IGFBP-4 and thus increase IGF bioavailability locally in the placenta, to promote IGF-II-mediat...

Irene Y C Sun, Michael T Overgaard, Claus Oxvig, Linda C Giudice (2002) J Clin Endocrinol Metab 87: 11 5235-5240

Pregnancy-associated plasma protein-A2 (PAPP-A2), a novel insulin-like growth factor-binding protein-5 proteinase.

2009-05-26T14:33:36Z

A novel metalloproteinase with similarity to pregnancy-associated plasma protein-A (PAPP-A), which we denoted PAPP-A2, has been identified. Through expression in mammalian cells we showed that recombinant PAPP-A2 polypeptide of 1558 residues resulted from processing of a 1791-residue prepro-protein. Unlike PAPP-A, PAPP-A2 migrated as a monomer (of 220 kDa) in non-reducing SDS-polyacrylamide gel el...

M T Overgaard, H B Boldt, L S Laursen, L Sottrup-Jensen, C A Conover, C Oxvig (2001) J Biol Chem 276: 24 21849-21853

Insulin-like growth factor binding protein-4 protease produced by smooth muscle cells increases in the coronary artery after angioplasty.

2009-05-26T14:33:36Z

Insulin-like growth factor (IGF)-I stimulates vascular smooth muscle cell (VSMC) migration and proliferation, which are fundamental to neointimal hyperplasia in postangioplasty restenosis. IGF-I action is modulated by several high-affinity IGF binding proteins (IGFBPs). IGFBP-4 is the predominant IGFBP produced by VSMCs and is a potent inhibitor of IGF-I action. However, specific IGFBP-4 proteases...

A Bayes-Genis, R S Schwartz, D A Lewis, M T Overgaard, M Christiansen, C Oxvig, K Ashai, D R Holmes, C A Conover (2001) Arterioscler Thromb Vasc Biol 21: 3 335-341

An isolated, surface-expressed I domain of the integrin alphaLbeta2 is sufficient for strong adhesive function when locked in the open conformation with a disulfide bond.

2009-05-26T14:33:36Z

We introduced disulfide bonds to lock the integrin alphaLbeta2 I domain in predicted open, ligand binding or closed, nonbinding conformations. Transfectants expressing alphaLbeta2 heterodimers containing locked-open but not locked-closed or wild-type I domains constitutively adhered to intercellular adhesion molecule-1 (ICAM-1) substrates. Locking the I domain closed abolished constitutive and act...

C Lu, M Shimaoka, M Ferzly, C Oxvig, J Takagi, T A Springer (2001) Proc Natl Acad Sci U S A 98: 5 2387-2392

Pregnancy-associated plasma protein-a is the insulin-like growth factor binding protein-4 protease secreted by human ovarian granulosa cells and is a marker of dominant follicle selection and the corpus luteum.

2009-05-26T14:33:36Z

Insulin-like growth factors (IGFs), IGF binding proteins (IGFBPs), and IGFBP proteases are important in ovarian function. IGFs stimulate granulosa steroidogenesis, an effect that is inhibited by IGFBP-4 and augmented by IGFBP-4 proteolysis. We have recently identified the IGFBP-4 protease in human ovarian follicular fluid (FF) as pregnancy-associated plasma protein-A (PAPP-A). In the current study...

C A Conover, G F Faessen, K E Ilg, Y A Chandrasekher, M Christiansen, M T Overgaard, C Oxvig, L C Giudice (2001) Endocrinology 142: 5

Pregnancy-associated plasma protein-A (PAPP-A) in ovine, bovine, porcine, and equine ovarian follicles: involvement in IGF binding protein-4 proteolytic degradation and mRNA expression during follicular development.

2009-05-26T14:33:36Z

IGF binding protein-4 (IGFBP-4) proteolytic degradation is a common feature of preovulatory follicles from human, ovine, bovine, porcine, and equine ovary. In all these species, the protease is a zinc-dependent metalloprotease and its ability to degrade IGFBP-4 is IGF dependent. The human intrafollicular IGFBP-4-degrading protease has recently been identified as pregnancy-associated plasma protein...

S Mazerbourg, M T Overgaard, C Oxvig, M Christiansen, C A Conover, I Laurendeau, M Vidaud, G Tosser-Klopp, J Zapf, P Monget (2001) Endocrinology 142: 12 5243-5253

Mutational analysis of the proteolytic domain of pregnancy-associated plasma protein-A (PAPP-A): classification as a metzincin.

2009-05-26T14:33:36Z

The bioavailability of insulin-like growth factor (IGF)-I and -II is controlled by six IGF-binding proteins (IGFBPs 1-6). Bound IGF is not active, but proteolytic cleavage of the binding protein causes release of IGF. Pregnancy-associated plasma protein-A (PAPP-A) has recently been found to cleave IGFBP-4 in an IGF-dependent manner. To experimentally support the hypothesis that PAPP-A belongs to t...

H B Boldt, M T Overgaard, L S Laursen, K Weyer, L Sottrup-Jensen, C Oxvig (2001) Biochem J 358: Pt 2 359-367

Pregnancy-associated plasma protein A as a marker of acute coronary syndromes.

2009-05-26T14:33:36Z

BACKGROUND: Circulating markers indicating the instability of atherosclerotic plaques could have diagnostic value in unstable angina or acute myocardial infarction. We evaluated pregnancy-associated plasma protein A (PAPP-A), a potentially proatherosclerotic metalloproteinase, as a marker of acute coronary syndromes. METHODS: We examined the level of expression of PAPP-A in eight culprit unstable ...

A Bayes-Genis, C A Conover, M T Overgaard, K R Bailey, M Christiansen, D R Holmes, R Virmani, C Oxvig, R S Schwartz (2001) N Engl J Med 345: 14 1022-1029

Pregnancy-associated plasma protein-A (PAPP-A) cleaves insulin-like growth factor binding protein (IGFBP)-5 independent of IGF: implications for the mechanism of IGFBP-4 proteolysis by PAPP-A.

2009-05-26T14:33:36Z

Pregnancy-associated plasma protein-A (PAPP-A) has recently been identified as the proteinase responsible for cleavage of insulin-like growth factor binding protein (IGFBP)-4, an inhibitor of IGF action, in several biological fluids. Cleavage of IGFBP-4 by PAPP-A is believed to occur only in the presence of IGF. We here report that in addition to IGFBP-4, PAPP-A also cleaves IGFBP-5. Cleavage occu...

L S Laursen, M T Overgaard, R Søe, H B Boldt, L Sottrup-Jensen, L C Giudice, C A Conover, C Oxvig (2001) FEBS Lett 504: 1-2 36-40

The status of half-cystine residues and locations of N-glycosylated asparagine residues in human eosinophil peroxidase.

2009-05-26T14:33:36Z

The determination by protein chemistry methods of the half-cystine status in human eosinophil peroxidase (EPO) is reported. EPO is two-chained and has a total of 14 half-cystine residues. Cys141 and Cys152 form an intrachain bridge in the light chain of EPO. Disulfide bridges connect Cys253 and Cys263, Cys257 and Cys287, Cys359 and Cys370, Cys570 and Cys635, and Cys676 and Cys701, forming five int...

A R Thomsen, L Sottrup-Jensen, G J Gleich, C Oxvig (2000) Arch Biochem Biophys 379: 1 147-152

Expression of recombinant human pregnancy-associated plasma protein-A and identification of the proform of eosinophil major basic protein as its physiological inhibitor.

2009-05-26T14:33:36Z

Pregnancy-associated plasma protein-A (PAPP-A), originally known from human pregnancy serum, has recently been demonstrated to be a metzincin superfamily metalloproteinase involved in normal and pathological insulin-like growth factor (IGF) physiology. PAPP-A specifically cleaves IGF-binding protein (IGFBP)-4, one of six antagonists of IGF action, which results in release of IGF bound to IGFBP-4. ...

M T Overgaard, J Haaning, H B Boldt, I M Olsen, L S Laursen, M Christiansen, G J Gleich, L Sottrup-Jensen, C A Conover, C Oxvig (2000) J Biol Chem 275: 40 31128-31133

Folding and function of I domain-deleted Mac-1 and lymphocyte function-associated antigen-1.

2009-05-26T14:33:36Z

In those integrins that contain it, the I domain is a major ligand recognition site. The I domain is inserted between beta-sheets 2 and 3 of the predicted beta-propeller domain of the integrin alpha subunit. We deleted the I domain from the integrin alpha(M) and alpha(L) subunits to give I-less Mac-1 and lymphocyte function-associated antigen-1 (LFA-1), respectively. The I-less alpha(M) and alpha(...

P Yalamanchili, C Lu, C Oxvig, T A Springer (2000) J Biol Chem 275: 29 21877-21882

Quantification and characterization of pregnancy-associated complexes of angiotensinogen and the proform of eosinophil major basic protein in serum and amniotic fluid.

2009-05-26T14:33:36Z

BACKGROUND: The proform of eosinophil major basic protein (ProMBP) exists in serum from pregnant women complexed with a variable fraction of angiotensinogen (Ang). A subfraction further binds complement C3dg in a 2:2:2 complex. The function, physiology, and clinical importance of ProMBP complexes are unknown, and the specific quantification of these complexes has not been possible. METHODS: We dev...

M Christiansen, I Jaliashvili, M T Overgaard, C Ensinger, P Obrist, C Oxvig (2000) Clin Chem 46: 8 Pt 1 1099-1105

Regulation of human ADAM 12 protease by the prodomain. Evidence for a functional cysteine switch.

2009-05-26T14:33:36Z

The ADAMs (a disintegrin and metalloprotease) are a family of multidomain proteins that are believed to play key roles in cell-cell and cell-matrix interactions. We have shown recently that human ADAM 12-S (meltrin alpha) is an active metalloprotease. It is synthesized as a zymogen, with the prodomain maintaining the protease in a latent form. We now provide evidence that the latency mechanism of ...

F Loechel, M T Overgaard, C Oxvig, R Albrechtsen, U M Wewer (1999) J Biol Chem 274: 19 13427-13433

The insulin-like growth factor (IGF)-dependent IGF binding protein-4 protease secreted by human fibroblasts is pregnancy-associated plasma protein-A.

2009-05-26T14:33:36Z

Proteolytic cleavage of the six known insulin-like growth factor binding proteins (IGFBPs) is a powerful means of rapid structure and function modification of these important growth-regulatory proteins. Intact IGFBP-4 is a potent inhibitor of IGF action in vitro, and cleavage of IGFBP-4 has been shown to abolish its ability to inhibit IGF stimulatory effects in a variety of systems, suggesting tha...

J B Lawrence, C Oxvig, M T Overgaard, L Sottrup-Jensen, G J Gleich, L G Hays, J R Yates, C A Conover (1999) Proc Natl Acad Sci U S A 96: 6 3149-3153

Conformational changes in tertiary structure near the ligand binding site of an integrin I domain.

2009-05-26T14:33:36Z

For efficient ligand binding, integrins must be activated. Specifically, a conformational change has been proposed in a ligand binding domain present within some integrins, the inserted (I) domain [Lee, J., Bankston, L., Arnaout, M. & Liddington, R. C. (1995) Structure (London) 3, 1333-1340]. This proposal remains controversial, however, despite extensive crystal structure studies on the I domain ...

C Oxvig, C Lu, T A Springer (1999) Proc Natl Acad Sci U S A 96: 5 2215-2220

Biochemical evidence for heme linkage through esters with Asp-93 and Glu-241 in human eosinophil peroxidase. The ester with Asp-93 is only partially formed in vivo.

2009-05-26T14:33:36Z

The covalent heme attachment has been extensively studied by spectroscopic methods in myeloperoxidase and lactoperoxidase (LPO) but not in eosinophil peroxidase (EPO). We show that heme linkage to the heavy chain is invariably present, whereas heme linkage to the light chain of EPO is present in less than one-third of EPO molecules. Mass analysis of isolated heme bispeptides supports the hypothesi...

C Oxvig, A R Thomsen, M T Overgaard, E S Sorensen, P Højrup, M J Bjerrum, G J Gleich, L Sottrup-Jensen (1999) J Biol Chem 274: 24 16953-16958

Messenger ribonucleic acid levels of pregnancy-associated plasma protein-A and the proform of eosinophil major basic protein: expression in human reproductive and nonreproductive tissues.

2009-05-26T14:33:36Z

PAPP-A/proMBP, the complex of pregnancy-associated plasma protein-A (PAPP-A) and the proform of eosinophil major basic protein (proMBP), circulates at increasing levels during pregnancy. The major site of synthesis is the placenta, in which PAPP-A mRNA has been localized to the syncytiotrophoblast and the placental X cells, whereas proMBP mRNA has been localized to the placental X cells only. The ...

M T Overgaard, C Oxvig, M Christiansen, J B Lawrence, C A Conover, G J Gleich, L Sottrup-Jensen, J Haaning (1999) Biol Reprod 61: 4 1083-1089

Evidence that the insulin-like growth factor binding protein-4 protease in human ovarian follicular fluid is pregnancy associated plasma protein-A.

2009-05-26T14:33:36Z

Ovarian insulin-like growth factor binding protein-4 (IGFBP-4) proteolysis is involved in the regulation of follicular development, but until now the identity of the responsible enzyme was unknown. In this study, we identify the IGFBP4 protease in human follicular fluid as pregnancy associated plasma protein-A (PAPP-A) based on distinctive IGFBP-4 cleavage pattern, the same protease inhibitor prof...

C A Conover, C Oxvig, M T Overgaard, M Christiansen, L C Giudice (1999) J Clin Endocrinol Metab 84: 12 4742-4745

The proform of eosinophil major basic protein: a new maternal serum marker for Down syndrome.

2009-05-26T14:33:36Z

The proform of eosinophil major basic protein (proMBP), the most abundant protein in the eosinophil specific granule, is synthesized by the placenta and secreted into the maternal circulation, where it is found complex-bound to pregnancy-associated plasma protein-A (PAPP-A) and other proteins. We examined the potential of proMBP as a maternal serum marker for fetal Down syndrome (DS) by determinin...

M Christiansen, C Oxvig, J M Wagner, Q P Qin, T H Nguyen, M T Overgaard, S O Larsen, L Sottrup-Jensen, G J Gleich, B Norgaard-Pedersen (1999) Prenat Diagn 19: 10 905-910

The structure of the beta-propeller domain and C-terminal region of the integrin alphaM subunit. Dependence on beta subunit association and prediction of domains.

2009-05-26T14:33:36Z

The alphaM subunit of integrin Mac-1 contains several distinct regions in its extracellular segment. The N-terminal region has been predicted to fold into a beta-propeller domain composed of seven beta-sheets each about 60 amino acid residues long, with the I-domain inserted between beta-sheets 2 and 3. The structure of the C-terminal region is unknown. We have used monoclonal antibodies (mAbs) as...

C Lu, C Oxvig, T A Springer (1998) J Biol Chem 273: 24 15138-15147

Experimental support for a beta-propeller domain in integrin alpha-subunits and a calcium binding site on its lower surface.

2009-05-26T14:33:36Z

Integrins are large, heterodimeric surface molecules of wide importance in cell adhesion. The N-terminal half of all integrin alpha-subunits contains seven weak sequence repeats of approximately 60 amino acids that are important in ligand binding and have been predicted to fold cooperatively into a single beta-propeller domain with seven beta-sheets. We provide evidence supporting this model with ...

C Oxvig, T A Springer (1998) Proc Natl Acad Sci U S A 95: 9 4870-4875

Double-monoclonal immunofluorometric assays for pregnancy-associated plasma protein A/proeosinophil major basic protein (PAPP-A/proMBP) complex in first-trimester maternal serum screening for Down syndrome.

2009-05-26T14:33:36Z

Four double-monoclonal time-resolved immunofluorometric assays (TrIFMAs) have been developed for the specific determination of pregnancy-associated plasma protein A/proeosinophil major basic protein (PAPP-A/ proMBP) complex in first-trimester maternal serum samples. The assays have a functional sensitivity of < 4 mIU/L and a working range from 4 to 1000 mIU/L. These 4 assays, together with a polyc...

Q P Qin, M Christiansen, C Oxvig, K Pettersson, L Sottrup-Jensen, C Koch, B Nørgaard-Pedersen (1997) Clin Chem 43: 12 2323-2332

Simple and reliable procedure for PCR amplification of genomic DNA from yeast cells using short sequencing primers.

2009-05-26T14:33:36Z

Yeast is widely used in molecular biology. Heterologous expression of recombinant proteins in yeast involves screening of a large number of recombinants. We present an easy and reliable procedure for amplifying genomic DNA from freshly grown cells of the methylotrophic yeast Pichia pastoris by means of PCR without any prior DNA purification steps. This method involves a simple boiling step of whol...

J Haaning, C Oxvig, M T Overgaard, L Sottrup-Jensen (1997) Biochem Mol Biol Int 42: 1 169-172

Complete cDNA sequence of the preproform of human pregnancy-associated plasma protein-A. Evidence for expression in the brain and induction by cAMP.

2009-05-26T14:33:36Z

A cDNA that encodes the prepropeptide of pregnancy-associated plasma protein-A (preproPAPP-A), a putative metalloproteinase, has been cloned and sequenced. PAPP-A is synthesized in the placenta as a 1627-residue precursor preproprotein with a putative 22-residue signal peptide and a highly basic propeptide of 58 residues. The prepro-PAPP-A-encoding transcript contains a region with an extremely hi...

J Haaning, C Oxvig, M T Overgaard, P Ebbesen, T Kristensen, L Sottrup-Jensen (1996) Eur J Biochem 237: 1 159-163

Identification of angiotensinogen and complement C3dg as novel proteins binding the proform of eosinophil major basic protein in human pregnancy serum and plasma.

2009-05-26T14:33:36Z

In sera from pregnant women, pregnancy-associated plasma protein-A (PAPP-A) circulates as a disulfide-bound complex (approximately 474 kDa) with the proform of eosinophil major basic protein (proMBP) (Oxvig, C., Sand, O., Kristensen, T., Gleich, G. J., and Sottrup-Jensen, L. (1993) J. Biol. Chem. 268, 12243-12246). We have produced monoclonal antibodies (mAbs) against the PAPP-A.proMBP complex and...

C Oxvig, J Haaning, L Kristensen, J M Wagner, I Rubin, T Stigbrand, G J Gleich, L Sottrup-Jensen (1995) J Biol Chem 270: 23 13645-13651

Localization of disulfide bridges and free sulfhydryl groups in human eosinophil granule major basic protein.

2009-05-26T14:33:36Z

Eosinophil granule major basic protein (117 residues) is known to contain free sulfhydryl groups. Here we have located in the amino acid sequence the half-cystine residues present as cysteine, and identified those engaged in disulfide bridges. Of the 9 half-cystine residues, 5 are unpaired cysteines (Cys2, Cys23, Cys42, Cys64, and Cys96), while 4 form disulfides (Cys20-Cys115, and Cys92-Cys107).

C Oxvig, G J Gleich, L Sottrup-Jensen (1994) FEBS Lett 341: 2-3 213-217

Amino acid sequence of human pregnancy-associated plasma protein-A derived from cloned cDNA.

2009-05-26T14:33:36Z

The amino acid sequence of human pregnancy-associated plasma protein-A (PAPP-A), a component of the circulating complex with the proform of eosinophil major basic protein (proMBP), has been determined from partial protein sequencing and from sequencing of cloned cDNA. The PAPP-A monomer contains 1547 amino acid residues, but is derived from a larger precursor of placental origin. PAPP-A contains 8...

T Kristensen, C Oxvig, O Sand, N P Møller, L Sottrup-Jensen (1994) Biochemistry 33: 6 1592-1598

Location and nature of carbohydrate groups in proform of human major basic protein isolated from pregnancy serum.

2009-05-26T14:33:36Z

From human pregnancy serum we have isolated the proform of eosinophil major basic protein (proMBP), which forms a complex with pregnancy-associated plasma protein-A (PAPP-A), PAPP-A/proMBP. It is shown that proMBP contains O-linked glycan bound to Ser-24, Thr-25 (fully substituted), and to Thr-23 and Thr-34 (partially substituted). N-linked glycan is bound to Asn-86 and O-linked glycosaminoglycan ...

C Oxvig, J Haaning, P Højrup, L Sottrup-Jensen (1994) Biochem Mol Biol Int 33: 2 329-336

Isolation and characterization of circulating complex between human pregnancy-associated plasma protein-A and proform of eosinophil major basic protein.

2009-05-26T14:33:36Z

The plasma protein previously known as pregnancy associated plasma protein-A (PAPP-A) and believed to contain only one kind of polypeptide chain has recently been shown to be a complex containing two different chains in equimolar amounts. One of the chains is now defined as the PAPP-A subunit, and the other has been identified as the proform of eosinophil major basic protein (proMBP) (Oxvig et al....

C Oxvig, O Sand, T Kristensen, L Kristensen, L Sottrup-Jensen (1994) Biochim Biophys Acta 1201: 3 415-423

Localization of pregnancy-associated plasma protein-A and colocalization of pregnancy-associated plasma protein-A messenger ribonucleic acid and eosinophil granule major basic protein messenger ribonucleic acid in placenta.

2009-05-26T14:33:36Z

BACKGROUND: The human eosinophil granule major basic protein (MBP), a 13.8 kilodalton cationic polypeptide constituting the core of the eosinophil granule, is cytotoxic to parasites and numerous mammalian cells. Concentrations of a molecule immunochemically similar to eosinophil granule MBP are present in maternal plasma, and MBP mRNA has been localized to placental X cells by in situ hybridizatio...

M Bonno, C Oxvig, G M Kephart, J M Wagner, T Kristensen, L Sottrup-Jensen, G J Gleich (1994) Lab Invest 71: 4 560-566

Biochemical properties, activities, and presence in biologic fluids of eosinophil granule major basic protein.

2009-05-26T14:33:36Z

The existence of a proform of MBP is predicted from the sequence of MBP cDNA clones. ProMBP has been purified from the supernatants of CHO cells transfected with cDNA encoding prepro MBP. Purification involved heparin-Sepharose affinity purification followed by two sequential size fractionation steps over Sephadex G-100 and yielded proMBP with a molecular mass of 33 kd. Recombinant proMBP from the...

P Popken-Harris, L Thomas, C Oxvig, L Sottrup-Jensen, H Kubo, J S Klein, G J Gleich (1994) J Allergy Clin Immunol 94: 6 Pt 2 1282-1289

Circulating human pregnancy-associated plasma protein-A is disulfide-bridged to the proform of eosinophil major basic protein.

2009-05-26T14:33:36Z

A previously unrecognized association between pregnancy-associated plasma protein-A (PAPP-A) and the proform of eosinophil major basic protein (proMBP) is demonstrated. PAPP-A isolated from pooled pregnancy serum is shown to be a disulfide-bridged complex with proMBP (PAPP-A/proMBP) in which the subunits of the constituents are present in a 1:1 molar ratio. The results are the outcome of analysis ...

C Oxvig, O Sand, T Kristensen, G J Gleich, L Sottrup-Jensen (1993) J Biol Chem 268: 17 12243-12246