Endogenous IGFBP-3 is protected from inducible IGFBP-3 protease activity in normal adult serum

Maile, Laura A.; Whellams, E.J.; Holly, Jeff M.P.

doi:10.1054/ghir.2000.0142

Cited by 4 publications

(3 citation statements)

References 18 publications

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“…However we used a serum:IGFBP-1 ratio that was more than 20-fold less than that in the circulation, suggesting that such changes would need to be at least of that magnitude. Similarly, IGFBP-3 proteases are inhibited by serum inhibitors [27] and it has been proposed that specific degradation of IGFBP-3 [28] and IGFBP-4 [29] occur at the tissue level to increase local IGF action. Azurocidin is mobilized from neutrophil secretory granules in response to inflammation [30].…”

Section: Discussionmentioning

confidence: 99%

IGFBP-1 protease activity and IGFBP-1 fragments in a patient with multiple myeloma

Brandt¹,

Wang²,

Lundell³

et al. 2009

Growth Hormone & IGF Research

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Section: Discussionmentioning

confidence: 99%

IGFBP-1 protease activity and IGFBP-1 fragments in a patient with multiple myeloma

Brandt¹,

Wang²,

Lundell³

et al. 2009

Growth Hormone & IGF Research

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“…The basic sequence 215-232 of IGFBP-3, close to the identified cleavage site, contains heparin, ALS and IGF-I binding sites as well as a nuclear localization site [22]. Interestingly, heparin has been reported to modulate IGFBP-3 proteolysis in pregnancy serum [19] as well as in non-pregnancy serum [33]. Durham et al [34] demonstrated that prekallekrein degrades IGFBP-3 and that a peptide identical to the heparin-binding domain of IGFBP-3 inhibits IGFBP-3 binding to the protease.…”

Section: Discussionmentioning

confidence: 99%

A 30-kDa fragment of insulin-like growth factor (IGF) binding protein-3 in human pregnancy serum with strongly reduced IGF-I binding

Ahlsén

Carlsson-Skwirut

Jönsson

et al. 2007

Cell. Mol. Life Sci.

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Proteolytic cleavage of insulin-like growth factor (IGF) binding protein (IGFBP)-3 during pregnancy is likely to have both IGF-dependent and -independent effects on maternal, placental and fetal growth and metabolism. A 30-kDa proteolytic IGFBP-3 fragment was isolated from third trimester pregnancy human serum and identified by N- and C-terminal amino acid sequence analysis and mass spectrometry to correspond to residues 1-212 of the parent protein. This fragment is the dominating IGFBP-3 immunoreactive species in pregnancy serum. The 30-kDa fragment was also detected in serum of non-pregnant women where it coexists with intact IGFBP-3. Using biosensor technology, (1-212)IGFBP-3 was found to have 11-fold lower affinity for IGF-I compared to intact IGFBP-3, while a 4-fold decrease in affinity was found for IGF-II. Tests with des(1-3)IGF-I suggest fast binding of IGF-I to the N-terminal region of IGFBP-3 and similar affinity to a slow binding site in the C-terminal region.

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“…The former assumption is supported by the detection of the nonrelated protease inhibitor antithrombin III in the eluate, which might contain other natural serine protease inhibitors. On the other hand, Holly and collaborators (37,38) have provided evidence for the presence of components protecting IGFBP-3 in normal serum from proteolysis. Their data suggest that the accessibility of the C-terminal basic heparin-binding domain of IGFBP-3 is necessary for proteolysis or for binding of an inhibitor.…”

Section: Discussionmentioning

confidence: 99%

Interaction of Insulin-like Growth Factor II (IGF-II) with Multiple Plasma Proteins

Oesterreicher

Blum

Schmidt

et al. 2005

Journal of Biological Chemistry

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In the circulation, most of the insulin-like growth factors (IGFs), IGF-binding proteins (IGFBPs), and IGFBP proteases are bound in high molecular mass complexes of >150 kDa. To investigate molecular interactions between proteins involved in IGF⅐IGFBP complexes, Cohn fraction IV of human plasma was subjected to IGF-II affinity chromatography followed by reversed-phase high pressure liquid chromatography and analysis of bound proteins. Mass spectrometry and Western blotting revealed the presence of IGFBP-3, IGFBP-5, transferrin, plasminogen, prekallikrein, antithrombin III, and the soluble IGF-II/mannose 6-phosphate receptor in the eluate. Furthermore, an IGFBP-3 protease cleaving also IGFBP-2 but not IGFBP-4 was co-purified from the IGF-II column. Inhibitor studies and IGFBP-3 zymography have demonstrated that the 92-kDa IGFBP-3 protease belongs to the class of serine-dependent proteases. IGF-II ligand blotting and surface plasmon resonance spectrometry have been used to identify plasminogen as a novel high affinity IGF-II-binding protein capable of binding to IGFBP-3 with 50-fold higher affinity than transferrin. In combination with transferrin, the overall binding constant of plasminogen/transferrin for IGF-II was reduced 7-fold. Size exclusion chromatography of the IGF-II matrix eluate revealed that transferrin, plasminogen, and the IGFBP-3 protease are present in different high molecular mass complexes of >440 kDa. The present data indicate that IGFs, low and high affinity IGFBPs, several IGFBP-associated proteins, and IGFBP proteases can interact, which may result in the formation of binary, ternary, and higher molecular weight complexes capable of modulating IGF binding properties and the stability of IGFBPs. The insulin-like growth factors (IGF-I and IGF-II)1 are important regulators of growth, differentiation, and survival.Both their mitogenic and metabolic effects are for the most part mediated through binding and activation of the IGF-I receptor (1). The interaction of IGFs with the IGF-I receptor is controlled by a family of six high affinity IGF-binding proteins (IGFBP-1 to IGFBP-6) exhibiting strong sequence homology. The cysteine-rich N-and C-terminal domains are conserved across all IGFBPs, and both domains appear to be involved in IGF binding (2, 3). In the circulation, the majority of the IGFs are sequestered into ternary 150-kDa complexes with either IGFBP-3 or IGFBP-5 and the 85-kDa acid-labile subunit, prolonging the half-life of IGFs, controlling their transcapillary transport to the target tissues, and functioning as a circulating reservoir of IGFs (4 -6). The IGFBPs can also form binary complexes with IGFs. Limited proteolysis of IGFBPs appears to be the major mechanism for the release of IGFs from binary and ternary IGFBP complexes, resulting in the generation of IGFBP fragments with reduced affinities for IGFs (7,8). Several cation-and serine-dependent serum proteases, such as a disintegrin and metalloprotease (ADAM) 12S, matrix metalloprotease-3, ␣-kallikrein, plasmin, thrombin, and the...

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Endogenous IGFBP-3 is protected from inducible IGFBP-3 protease activity in normal adult serum

Cited by 4 publications

References 18 publications

IGFBP-1 protease activity and IGFBP-1 fragments in a patient with multiple myeloma

IGFBP-1 protease activity and IGFBP-1 fragments in a patient with multiple myeloma

A 30-kDa fragment of insulin-like growth factor (IGF) binding protein-3 in human pregnancy serum with strongly reduced IGF-I binding

Interaction of Insulin-like Growth Factor II (IGF-II) with Multiple Plasma Proteins

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