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†

Biochemistry ◽  
2007 ◽  
Vol 46 (7) ◽  
pp. 1972-1980 ◽  
Author(s):  
Claus Gyrup ◽  
Claus Oxvig
Keyword(s):  
Quantitative Analysis ◽  
Growth Factor ◽  
Plasma Protein ◽  
Binding Protein ◽  
Protein A ◽  
Insulin Like Growth Factor ◽  
Factor Binding

scholarly journals Studies on regulation of IGF (insulin-like growth factor)-binding protein (IGFBP) 4 proteolysis by pregnancy-associated plasma protein-A (PAPP-A) in cells treated with phorbol ester

2004 ◽  
Vol 379 (1) ◽  
pp. 57-64 ◽  
Author(s):  
Arun S. SIVANANDAM ◽  
Subburaman MOHAN ◽  
Hirohito KITA ◽  
Sanjay KAPUR ◽  
Shin-Tai CHEN ◽  
...  
Keyword(s):  
Growth Factor ◽  
Proteolytic Activity ◽  
Plasma Protein ◽  
Binding Protein ◽  
Protein A ◽  
Insulin Like Growth Factor ◽  
Factor Binding ◽  
Fold Reduction ◽  
Sds Page ◽  
Eosinophil Major Basic Protein

PAPP-A (pregnancy-associated plasma protein-A) is produced by hSFs (human skin fibroblasts) and hOBs (human osteoblasts) and enhances the mitogenic activity of IGFs (insulin-like growth factors) by degradation of IGFBP-4 (insulin-like growth factor-binding protein 4). PKC (protein kinase C) activation in these cells led to reduction in IGFBP-4 proteolysis. This study was undertaken to determine the mechanism by which activation of PKC suppresses IGFBP-4 proteolysis. Treatment of hSFs/hOBs with TPA (PMA; 100 nM) reduced IGFBP-4 proteolysis without significantly decreasing the PAPP-A level in the CM (conditioned medium). Immunodepletion of the proform of eosinophil major basic protein (proMBP), a known PAPP-A inhibitor, from CM of TPA-treated cells (TPA CM) failed to increase IGFBP-4 proteolytic activity. Transduction of hSFs with proMBP retrovirus increased the concentration of proMBP up to 30 ng/ml and led to a moderate reduction in IGFBP-4 proteolysis. In contrast, TPA treatment blocked IGFBP-4 proteolysis but failed to induce a detectable amount of proMBP in the CM. While proMBP overexpression led to the formation of a covalent proMBP–PAPP-A complex and reduced the migration of PAPP-A on SDS/PAGE, TPA treatment dose- and time-dependently increased the conversion of a ≈470 kDa PAPP-A form (PAPP-A470) to a ≈400 kDa PAPP-A form (PAPP-A400). Since unreduced PAPP-A400 co-migrated with the 400 kDa recombinant PAPP-A homodimer and since PAPP-A monomers from reduced PAPP-A470 and PAPP-A400 co-migrated on SDS/PAGE, conversion of PAPP-A470 to PAPP-A400 is unlikely to be caused by proteolytic cleavage of PAPP-A. Consistent with the data showing that the increase in the ratio of PAPP-A400/PAPP-A470 is correlated with the extent of reduction in IGFBP-4 proteolysis, partially purified PAPP-A400 exhibited a 4-fold reduction in IGFBP-4 proteolytic activity compared with PAPP-A470. These data suggest that a novel mechanism, namely conversion of PAPP-A470 to the less-active PAPP-A400, could account for the TPA-induced suppression of PAPP-A activity.

scholarly journals Insulin- like Growth Factor-Binding Protein Action in Bone Tissue: A Key Role for Pregnancy- Associated Plasma Protein-A

2018 ◽  
Vol 9 ◽  
Author(s):  
James Beattie ◽  
Hasanain Al-Khafaji ◽  
Pernille R. Noer ◽  
Hanaa Esa Alkharobi ◽  
Aishah Alhodhodi ◽  
...  
Keyword(s):  
Growth Factor ◽  
Bone Tissue ◽  
Plasma Protein ◽  
Binding Protein ◽  
Protein A ◽  
Insulin Like Growth Factor ◽  
Factor Binding

scholarly journals Corrigendum: Insulin- like Growth Factor-Binding Protein Action in Bone Tissue: A Key Role for Pregnancy- Associated Plasma Protein-A

2018 ◽  
Vol 9 ◽  
Author(s):  
James Beattie ◽  
Hasanain Al-Khafaji ◽  
Pernille R. Noer ◽  
Hanaa Esa Alkharobi ◽  
Aishah Alhodhodi ◽  
...  
Keyword(s):  
Growth Factor ◽  
Bone Tissue ◽  
Plasma Protein ◽  
Binding Protein ◽  
Protein A ◽  
Insulin Like Growth Factor ◽  
Factor Binding

scholarly journals 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

FEBS Letters ◽  
2001 ◽  
Vol 504 (1-2) ◽  
pp. 36-40 ◽  
Author(s):  
Lisbeth S. Laursen ◽  
Michael T. Overgaard ◽  
Rikke Søe ◽  
Henning B. Boldt ◽  
Lars Sottrup-Jensen ◽  
...  
Keyword(s):  
Growth Factor ◽  
Plasma Protein ◽  
Binding Protein ◽  
Protein A ◽  
Insulin Like Growth Factor ◽  
Factor Binding

scholarly journals Insulin-Like Growth Factor Bioactivity, Stanniocalcin-2, Pregnancy-Associated Plasma Protein-A, and IGF-Binding Protein-4 in Pleural Fluid and Serum From Patients With Pulmonary Disease

2017 ◽  
Vol 102 (9) ◽  
pp. 3526-3534 ◽  
Author(s):  
Ulrick Skipper Espelund ◽  
Mette Bjerre ◽  
Rikke Hjortebjerg ◽  
Torben Riis Rasmussen ◽  
Anders Lundby ◽  
...  
Keyword(s):  
Growth Factor ◽  
Pleural Fluid ◽  
Plasma Protein ◽  
Binding Protein ◽  
Protein A ◽  
Insulin Like Growth Factor ◽  
Igf System ◽  
Igf Binding ◽  
Stanniocalcin 2 ◽  
Igf Binding Protein

Abstract Context Members of the insulin-like growth factor (IGF) system are primarily produced in the liver and secreted into the circulation, but they are also produced, recruited, and activated locally in tissues. Objective To compare activity and concentrations of IGF system components in pleural fluid and blood. Design Pathological pleural fluid, secondary to lung cancer or nonmalignant disease, and matching blood samples were collected from 24 patients ages 66.7 to 81.9 years. Methods IGF-related proteins and cytokine levels were measured by immunoassays or immunoblotting. Bioactive IGF was measured by an IGF-1 receptor phosphorylation assay. Results Total IGF-1 concentration did not differ between the compartments, but concentrations of free IGF-1 and bioactive IGF were more than threefold higher in pleural fluid than in corresponding serum samples (P = 0.0004), regardless of etiology. Median pregnancy-associated plasma protein-A (PAPP-A) and interleukin (IL)-6 levels were increased 47-fold and 143-fold, respectively, in pleural fluid compared with plasma (P < 0.0001). PAPP-A and IL-6 concentrations correlated positively (r = 0.46; P = 0.02). In pleural fluid, levels of PAPP-A–generated IGF binding protein-4 fragments correlated inversely with that of stanniocalcin-2 (r ≤ −0.42; P ≤ 0.05), a PAPP-A inhibitor; such correlations were absent in plasma. Conclusion Pathological pleural fluid is characterized by increased in vitro IGF bioactivity and elevated concentrations of PAPP-A, an IGF-activating proteinase. Thus, the tissue activity of the IGF system may differ substantially from that of the circulating IGF system. The correlation between IL-6 and PAPP-A indicates that inflammation plays a role in promoting local tissue IGF activity.

scholarly journals Pregnancy-associated Plasma Protein-A2 (PAPP-A2), a Novel Insulin-like Growth Factor-binding Protein-5 Proteinase

2001 ◽  
Vol 276 (24) ◽  
pp. 21849-21853 ◽  
Author(s):  
Michael T. Overgaard ◽  
Henning B. Boldt ◽  
Lisbeth S. Laursen ◽  
Lars Sottrup-Jensen ◽  
Cheryl A. Conover ◽  
...  
Keyword(s):  
Growth Factor ◽  
Plasma Protein ◽  
Binding Protein ◽  
Insulin Like Growth Factor ◽  
Factor Binding
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