Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Phosphoinositides and PIPs01:42

Phosphoinositides and PIPs

10.5K
Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
10.5K
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

10.9K
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
10.9K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

6.2K
The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
6.2K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

7.8K
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
7.8K
Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

3.8K
Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
3.8K
IP3/DAG Signaling Pathway01:11

IP3/DAG Signaling Pathway

15.8K
Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the  phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and...
15.8K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

High Expression of PAPP-A Predicts Poor Outcomes in Oestrogen Receptor-Positive Breast Cancer Patients.

Cancer medicine·2026
Same author

Myoglobin Affects Tissue-Specific Transcriptome, Heart Regeneration and Whole Animal Metabolic Rates.

FASEB journal : official publication of the Federation of American Societies for Experimental Biology·2026
Same author

The crazy ovary 2: a tribute to Ken McNatty.

Biology of reproduction·2025
Same author

STING signals to NF-κB from late endolysosomal compartments using IRF3 as an adaptor.

Nature immunology·2025
Same author

Genes Encoding Intracellular Signaling Proteins in Animals Originated Along with Metazoa and Chordata: Chance or Necessity?

Genome biology and evolution·2025
Same author

Genetic and Pharmacological Inhibition of PAPP-A Reduces Bleomycin-Induced Pulmonary Fibrosis in Aged Mice via Reduced IGF Signaling.

Aging biology·2025

Related Experiment Video

Updated: Mar 21, 2026

Mapping Dysfunctional Protein-Protein Interactions in Disease
09:39

Mapping Dysfunctional Protein-Protein Interactions in Disease

Published on: October 24, 2025

984

PAPP-A and the IGF system.

Philippe Monget1, Claus Oxvig2

  • 1Institut national de la recherche agronomique, physiologie de la reproduction et des comportements, 37380 Nouzilly, France.

Annales D'Endocrinologie
|May 9, 2016
PubMed
Summary
This summary is machine-generated.

Pregnancy-associated plasma protein-A (PAPP-A) is a metalloproteinase that regulates insulin-like growth factor (IGF) bioavailability by cleaving IGF binding proteins. Targeting PAPP-A offers a strategy to modulate IGF signaling in various tissues.

Keywords:
IGF, IGFBP, Protéine-A plasmatique (PAPP-A), Pappalysine, PAPP-A, Pro-MBP, StanniocalcineInsulin-like growth factor (IGF)Insulin-like growth factor binding protein (IGFBP)PappalysinPregnancy-associated plasma protein-A (PAPP-A)Proform of eosinophil major basic protein (pro-MBP)Stanniocalcin (STC)

More Related Videos

Author Spotlight: Advancements and Challenges in β-Cells Differentiation from Pluripotent Stem Cells
06:33

Author Spotlight: Advancements and Challenges in β-Cells Differentiation from Pluripotent Stem Cells

Published on: February 2, 2024

2.8K
Author Spotlight: Optimization of Ultrashort Peptide Matrices for Colorectal Cancer Organoids
10:23

Author Spotlight: Optimization of Ultrashort Peptide Matrices for Colorectal Cancer Organoids

Published on: May 3, 2024

1.6K

Related Experiment Videos

Last Updated: Mar 21, 2026

Mapping Dysfunctional Protein-Protein Interactions in Disease
09:39

Mapping Dysfunctional Protein-Protein Interactions in Disease

Published on: October 24, 2025

984
Author Spotlight: Advancements and Challenges in β-Cells Differentiation from Pluripotent Stem Cells
06:33

Author Spotlight: Advancements and Challenges in β-Cells Differentiation from Pluripotent Stem Cells

Published on: February 2, 2024

2.8K
Author Spotlight: Optimization of Ultrashort Peptide Matrices for Colorectal Cancer Organoids
10:23

Author Spotlight: Optimization of Ultrashort Peptide Matrices for Colorectal Cancer Organoids

Published on: May 3, 2024

1.6K

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Endocrinology

Background:

  • Pregnancy-associated plasma protein-A (PAPP-A) is a metalloproteinase initially identified as a placental protein.
  • PAPP-A is widely expressed and cleaves insulin-like growth factor binding proteins (IGFBPs), specifically IGFBP-2, -4, and -5.
  • It functions locally as a growth-promoting enzyme by releasing bioactive IGF near its receptor.

Purpose of the Study:

  • To elucidate the mechanisms regulating PAPP-A activity and its role in IGF bioavailability.
  • To explore PAPP-A as a potential therapeutic target for modulating IGF signaling.

Main Methods:

  • Investigated PAPP-A's enzymatic activity and substrate specificity (IGFBP-2, -4, -5).
  • Examined PAPP-A's interaction with glycosaminoglycans and inhibitors like pro-MBP and stanniocalcin-2 (STC2).
  • Utilized in vivo experiments to assess the role of IGFBP-4 as a key PAPP-A substrate.

Main Results:

  • PAPP-A specifically cleaves IGFBP-2, -4, and -5, influencing IGF bioavailability.
  • Pro-MBP and STC2 inhibit PAPP-A activity through complex formation.
  • IGFBP-4 is identified as the primary substrate for PAPP-A in regulating IGF bioavailability.
  • Regulation mechanisms include transcriptional control, competition with other IGFBPs, and proteolytic inhibition.

Conclusions:

  • PAPP-A plays a crucial role in modulating IGF bioavailability through specific IGFBP cleavage.
  • The interaction between PAPP-A and IGFBP-4 is key for regulating IGF signaling.
  • PAPP-A represents a viable therapeutic target for inhibiting IGF signaling driven by elevated PAPP-A activity.