Antigenic Constituents in Pregnancy Plasma which are Undetectable in Normal Non-Pregnant Female or Male Plasma

Gall, SA; Sp, Halbert

doi:10.1159/000230632

Cited by 53 publications

(20 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A single lot of immunoglobulin concentrate from appropriately absorbed hyperimmune rabbit antisera to human pregnancy plasma was prepared as previously described (1,2). It was stored at -20'C in aliquots of 2 ml, which was sufficient for one set of assays.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Measurement of Pregnancy-Associated Plasma Proteins during Human Gestation

Lin¹,

Halbert²,

Spellacy³

1974

J. Clin. Invest.

175

View full text Add to dashboard Cite

show abstract

Section: Methodsmentioning

confidence: 99%

“…Previous studies from our laboratory have revealed the existence of up to four pregnancy-associated plasma proteins (PAPP's)' in women during the 2nd and 3rd trimesters of normal gestation (1,2). These proteins differed from each other immunologically and in their physicochemical properties.…”

Section: Introductionmentioning

confidence: 99%

Measurement of Pregnancy-Associated Plasma Proteins during Human Gestation

Lin¹,

Halbert²,

Spellacy³

1974

J. Clin. Invest.

175

View full text Add to dashboard Cite

show abstract

“…This MP was originally identified in 1972 as an antigen present in human pregnancy plasma (Gall and Halbert, 1972). It is ubiquitously expressed and plays central roles in ovarian follicular development , myogenesis (Kumar et al, 2005), human embryo implantation (Giudice et al, 2002) and wound healing (Chen et al, 2003), as well as in atherosclerosis (Lawrence et al, 1999;Bayes-Genis et al, 2001a,b;Thorn and Khan, 2007), early foetal stages of Down's syndrome development and cancer.…”

Section: Introductionmentioning

confidence: 99%

Activity of ulilysin, an archaeal PAPP-A-related gelatinase and IGFBP protease

Tallant

García‐Castellanos

Marrero

et al. 2007

BCHM

View full text Add to dashboard Cite

Human growth and development are conditioned by insulin-like growth factors (IGFs), which have also implications in pathology. Most IGF molecules are sequestered by IGF-binding proteins (IGFBPs) so that exertion of IGF activity requires disturbance of these complexes. This is achieved by proteolysis mediated by IGFBP proteases, among which the best characterised is human PAPP-A, the first member of the pappalysin family of metzincins. We have previously identified and studied the only archaeal homologue found to date, Methanosarcina acetivorans ulilysin. This is a proteolytically functional enzyme encompassing a pappalysin catalytic domain and a pro-domain involved in maintenance of latency of the zymogen, proulilysin. Once activated, the protein hydrolyses IGFBP-2 to -6 and insulin chain b in vitro. We report here that ulilysin is also active against several other substrates, viz (azo)casein, azoalbumin, and extracellular matrix components. Ulilysin has gelatinolytic but not collagenolytic activity. Moreover, the proteolysis-resistant skeletal proteins actin and elastin are also cleaved, as is fibrinogen, but not plasmin and a1-antitrypsin from the blood coagulation cascade. Ulilysin develops optimal activity at pH 7.5 and strictly requires peptide bonds preceding an arginine residue, as determined by means of a novel fluorescence resonance energy transfer assay, thus pointing to biotechnological applications as an enzyme complementary to trypsin.These two authors contributed equally to this work. a

show abstract

“…Among these, human PAPP-A specifically inactivates IGFBPs (4 -6). This MP was originally identified as an antigen in human pregnancy plasma (7). It is ubiquitously expressed and plays central roles in ovarian follicular development, myogenesis, human embryo implantation, and wound healing (8).…”

mentioning

confidence: 99%

Molecular Analysis of Ulilysin, the Structural Prototype of a New Family of Metzincin Metalloproteases

Tallant¹,

García‐Castellanos²,

Seco

et al. 2006

Journal of Biological Chemistry

114

View full text Add to dashboard Cite

The metzincin clan encompasses several families of zinc-dependent metalloproteases with proven function both in physiology and pathology. They act either as broad spectrum protein degraders or as sheddases, operating through limited proteolysis. Among the structurally uncharacterized metzincin families are the pappalysins, of which the most thoroughly studied member is human pregnancy-associated plasma protein A (PAPP-A), a heavily glycosylated 170-kDa multidomain protein specifically cleaving insulin-like growth factor (IGF)-binding proteins (IGFBPs). Proulilysin is a 38-kDa archaeal protein that shares sequence similarity with PAPP-A but encompasses only the pro-domain and the catalytic domain. It undergoes calcium-mediated autolytic activation, and the mature protein adopts a three-dimensional structure with two subdomains separated by an active site cleft containing the catalytic zinc ion. This structure is reminiscent of human members of the adamalysin/ADAMs (a disintegrin and a metalloprotease) family of metzincins. A bound dipeptide yields information on the substrate specificity of ulilysin, which specifically hydrolyzes IGFBP-2 to -6, insulin, and extracellular matrix proteins but not IGFBP-1 or IGF-II. Accordingly, ulilysin has higher proteolytic efficiency and a broader substrate specificity than human PAPP-A. The structure of ulilysin represents a prototype for the catalytic domain of pappalysins. Insulin-like growth factors (IGF)-I and -II4 regulate human somatic growth and development. Their activity is also correlated with several diseases, including atherosclerosis, cardiovascular disease, diabetes, and cancer (1). Most circulating IGF molecules are sequestered in complexes with soluble IGF-binding proteins (IGFBP-1 to -6) (2). IGFBPs antagonize binding of IGFs to their receptors because of their much higher affinity, and they are thus carriers, mediators, and reservoirs of IGFs (3). IGFs are released from these complexes with IGFBP through proteolytic inactivation mediated by IGFBP proteases, which include serine proteinases, cysteine proteinases, and metalloproteases (MPs). Among these, human PAPP-A specifically inactivates IGFBPs (4 -6). This MP was originally identified as an antigen in human pregnancy plasma (7). It is ubiquitously expressed and plays central roles in ovarian follicular development, myogenesis, human embryo implantation, and wound healing (8). Mature PAPP-A is a glycosylated multidomain protein of 1,547 residues that specifically hydrolyzes human IGFBP-4 in an IGF-dependent manner. Only human IGFBP-5 and bovine and porcine IGFBP-2 have been identified as further substrates (6). In addition to its proteolytic domain, three Lin12-Notch repeats (LNR-1, -2, and -3), modules that regulate ligand-induced proteolytic cleavage of the Notch receptor, and five complement control protein modules (CCP1-5) have been identified (9). Human PAPP-A is the founding member of the pappalysin family of MPs, which further comprehends the paralogue PAPP-A2 (10) and has been included in the metzinc...

show abstract

Antigenic Constituents in Pregnancy Plasma which are Undetectable in Normal Non-Pregnant Female or Male Plasma

Cited by 53 publications

References 9 publications

Measurement of Pregnancy-Associated Plasma Proteins during Human Gestation

Measurement of Pregnancy-Associated Plasma Proteins during Human Gestation

Activity of ulilysin, an archaeal PAPP-A-related gelatinase and IGFBP protease

Molecular Analysis of Ulilysin, the Structural Prototype of a New Family of Metzincin Metalloproteases

Contact Info

Product

Resources

About