The role of PAPP-A in the IGF system: location, location, location

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The role of PAPP-A in the IGF system : location, location, location. / Oxvig, Claus.

In: Journal of Cell Communication and Signaling, Vol. 9, No. 2, 06.2015, p. 177-87.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

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Oxvig, C 2015, 'The role of PAPP-A in the IGF system: location, location, location', Journal of Cell Communication and Signaling, vol. 9, no. 2, pp. 177-87. https://doi.org/10.1007/s12079-015-0259-9

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Oxvig, Claus. / The role of PAPP-A in the IGF system : location, location, location. In: Journal of Cell Communication and Signaling. 2015 ; Vol. 9, No. 2. pp. 177-87.

Bibtex

@article{ee60882c2ac44738aaac95cd8837dcd9,
title = "The role of PAPP-A in the IGF system: location, location, location",
abstract = "Although discovered as a placental protein present abundantly in the circulation of pregnant women, pregnancy-associated plasma protein-A (PAPP-A) is widely expressed in multiple tissues. PAPP-A is a highly specific metalloproteinase binding tightly to glycosaminoglycans present on the surface of cells. By cleaving a subset of insulin-like growth factor binding proteins (IGFBPs), PAPP-A thus functions within tissues as a growth-promoting enzyme, releasing bioactive IGF in close proximity to the IGF receptor. IGFBP-4 is believed to be the principal PAPP-A substrate, and the focus in this review is on PAPP-A enzymatic activity and its role in the PAPP-A-IGFBP-4-IGF axis, which is subject to regulation at several different levels. These include e.g., transcriptional control, competing reactions potentially sequestering IGF from IGFBP-4 and hence antagonizing PAPP-A-mediated IGF activation, and proteolytic inhibition of PAPP-A. The latter may involve the protein stanniocalcin-2 (STC2), recently found to potently inhibit PAPP-A activity by forming a covalent complex with PAPP-A. PAPP-A or complex-bound variants may escape from pathological tissues into the circulation. It is emphasized that the potential use of PAPP-A as a diagnostic or predictive biomarker in nonpregnant individuals requires precise knowledge of analyte identity and assay specificity in addition to an appropriate material for standardization. Finally, PAPP-A may serve as a therapeutic target to indirectly inhibit IGF signaling in tissues where this is driven by increased PAPP-A activity. By taking advantage of the intricate interaction between PAPP-A and IGFBP-4, highly specific and selective inhibition of PAPP-A is possible.",
author = "Claus Oxvig",
year = "2015",
month = "6",
doi = "10.1007/s12079-015-0259-9",
language = "English",
volume = "9",
pages = "177--87",
journal = "Journal of Cell Communication and Signaling",
issn = "1873-9601",
publisher = "Springer Nature",
number = "2",

}

RIS

TY - JOUR

T1 - The role of PAPP-A in the IGF system

T2 - location, location, location

AU - Oxvig, Claus

PY - 2015/6

Y1 - 2015/6

N2 - Although discovered as a placental protein present abundantly in the circulation of pregnant women, pregnancy-associated plasma protein-A (PAPP-A) is widely expressed in multiple tissues. PAPP-A is a highly specific metalloproteinase binding tightly to glycosaminoglycans present on the surface of cells. By cleaving a subset of insulin-like growth factor binding proteins (IGFBPs), PAPP-A thus functions within tissues as a growth-promoting enzyme, releasing bioactive IGF in close proximity to the IGF receptor. IGFBP-4 is believed to be the principal PAPP-A substrate, and the focus in this review is on PAPP-A enzymatic activity and its role in the PAPP-A-IGFBP-4-IGF axis, which is subject to regulation at several different levels. These include e.g., transcriptional control, competing reactions potentially sequestering IGF from IGFBP-4 and hence antagonizing PAPP-A-mediated IGF activation, and proteolytic inhibition of PAPP-A. The latter may involve the protein stanniocalcin-2 (STC2), recently found to potently inhibit PAPP-A activity by forming a covalent complex with PAPP-A. PAPP-A or complex-bound variants may escape from pathological tissues into the circulation. It is emphasized that the potential use of PAPP-A as a diagnostic or predictive biomarker in nonpregnant individuals requires precise knowledge of analyte identity and assay specificity in addition to an appropriate material for standardization. Finally, PAPP-A may serve as a therapeutic target to indirectly inhibit IGF signaling in tissues where this is driven by increased PAPP-A activity. By taking advantage of the intricate interaction between PAPP-A and IGFBP-4, highly specific and selective inhibition of PAPP-A is possible.

AB - Although discovered as a placental protein present abundantly in the circulation of pregnant women, pregnancy-associated plasma protein-A (PAPP-A) is widely expressed in multiple tissues. PAPP-A is a highly specific metalloproteinase binding tightly to glycosaminoglycans present on the surface of cells. By cleaving a subset of insulin-like growth factor binding proteins (IGFBPs), PAPP-A thus functions within tissues as a growth-promoting enzyme, releasing bioactive IGF in close proximity to the IGF receptor. IGFBP-4 is believed to be the principal PAPP-A substrate, and the focus in this review is on PAPP-A enzymatic activity and its role in the PAPP-A-IGFBP-4-IGF axis, which is subject to regulation at several different levels. These include e.g., transcriptional control, competing reactions potentially sequestering IGF from IGFBP-4 and hence antagonizing PAPP-A-mediated IGF activation, and proteolytic inhibition of PAPP-A. The latter may involve the protein stanniocalcin-2 (STC2), recently found to potently inhibit PAPP-A activity by forming a covalent complex with PAPP-A. PAPP-A or complex-bound variants may escape from pathological tissues into the circulation. It is emphasized that the potential use of PAPP-A as a diagnostic or predictive biomarker in nonpregnant individuals requires precise knowledge of analyte identity and assay specificity in addition to an appropriate material for standardization. Finally, PAPP-A may serve as a therapeutic target to indirectly inhibit IGF signaling in tissues where this is driven by increased PAPP-A activity. By taking advantage of the intricate interaction between PAPP-A and IGFBP-4, highly specific and selective inhibition of PAPP-A is possible.

U2 - 10.1007/s12079-015-0259-9

DO - 10.1007/s12079-015-0259-9

M3 - Journal article

C2 - 25617049

VL - 9

SP - 177

EP - 187

JO - Journal of Cell Communication and Signaling

JF - Journal of Cell Communication and Signaling

SN - 1873-9601

IS - 2

ER -