Identification of Vitronectin as a Novel Insulin-Like Growth Factor-II Binding Protein

Upton, Zee; Webb, Helen; Hale, Kathryn; Yandell, Catherine; McMurtry, John P.; Francis, G L; Ballard, F. J.

doi:10.1210/en.140.6.2928

Cited by 24 publications

(16 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although not reviewed herein, IGFBP proteolysis represents a major regulatory mechanism in IGF-mediated processes both at the cellular and physiological levels. Finally (at least as included here) was the recent discovery in chickens that vitronectin is an IGF-II-selective, 70 kDa serum-binding protein by Upton et al (1999), who proposed that the complex may serve to bring IGF-II to cell ECM. Recently, Nam et al (2002) reported that vitronectin also binds IGFBP-5 with high affinity and that localization of IGFBP-5 within the ECM by vitronectin appears to modify cell responsiveness to IGF-I via modulation of IGFBP-5.…”

Section: Other Directions Of Research In the Comparative Endocrinologmentioning

confidence: 98%

Comparative endocrinology of the insulin-like growth factor-binding protein

Kelley¹,

Schmidt²,

Berg³

et al. 2002

Journal of Endocrinology

105

View full text Add to dashboard Cite

Emerging early in chordate evolution, the IGF-regulatory axis diverged from an insulin-like predecessor into a vertebrate regulatory system specializing in cell growth activation and allied anabolic functions. Essential to the divergence of the IGF and insulin systems was an early presence of soluble IGF-binding proteins (IGFBPs), which bind IGF peptides at much higher affinity than that of the insulin receptor but at comparable affinities to that of the IGF receptor. IGFBPs have no homology with IGF receptors. Instead, IGFBPs are a derived group of proteins within a superfamily of cysteine-rich growth factors, whose members are found throughout the animal taxa. While blocking IGF actions through the insulin receptor is a fundamental role, IGFBPs evolved within the vertebrate line into centralized, 'integrators' of the endocrine growth-regulatory apparatus. IGFBPs have substantial influences on the distribution and bioavailability of IGF peptides in the cellular and physiological environments, but they have a variety of other properties. The six principal mammalian IGFBPs exhibit an array of specialized properties that appear to be derived from a complex evolutionary history (including cell membrane association, interaction with proteins that post-translationally modify them, direct IGF-independent effects on cells, and others) and they are regulated by a diversity of 'outside' factors (e.g. other hormones, metabolic status, stress). Thus, IGFBPs are multifunctional integrators having diverse physiological 'agendas'. Much less is known about IGFBPs and their properties in the other vertebrate taxa. Increasingly, however, it is being recognized that they play equally important endocrine roles, in both conserved and non-conserved ways, when compared with those currently defined in mammals. This review highlights selected 'comparative aspects' in current IGFBP research, in an attempt to view this essential group of endocrine regulators from a wider, biological perspective.

show abstract

Section: Other Directions Of Research In the Comparative Endocrinologmentioning

confidence: 98%

Comparative endocrinology of the insulin-like growth factor-binding protein

Kelley¹,

Schmidt²,

Berg³

et al. 2002

Journal of Endocrinology

105

View full text Add to dashboard Cite

show abstract

“…Because neither preincubation of the ECM with a polyclonal anti-VN antibody nor removal of ECM/VNbound PAI-1 altered binding of TGF-␤ to ECM, it seems likely that TGF-␤ and VN form a complex that could prevent TGF-␤ from binding to other ligands in the ECM. In addition to TGF-␤1, other growth factors such as EGF, VEGF, and bFGF bound VN with variable efficiency, and this list was recently extended by the identification of VN as an insulin-like growth factor II binding protein (Upton et al, 1999). Furthermore, comparison of growth factor binding to the different VN isoforms revealed that multimeric forms of VN (predominantly present in the ECM and secreted by platelets) exhibit higher affinity than plasma VN for TGF-␤.…”

mentioning

confidence: 99%

Molecular Interactions and Functional Interference between Vitronectin and Transforming Growth Factor-β

Schoppet

Chavakis

Al-Fakhri

et al. 2002

Laboratory Investigation

View full text Add to dashboard Cite

SUMMARY:Different extracellular matrix proteins have been described as binding proteins for growth factors, influencing their storage or presentation towards cellular receptors. The multifunctional adhesive glycoprotein vitronectin (VN), which is found in the circulation and widely distributed throughout different tissues, has been implicated in the regulation of vascular cell functions, and these activities could be related to interactions with various growth factors. In vitro, soluble VN interfered with transforming growth factor-␤ (TGF-␤) binding to isolated extracellular matrix and was found to associate with TGF-␤1 and TGF-␤2 as well as with other growth factors such as vascular endothelial growth factor, epidermal growth factor, or basic fibroblast growth factor in a saturable manner. In particular, binding of TGF-␤ was maximal for the heparin-binding multimeric isoform of VN, whereas VN in a ternary complex with thrombin and antithrombin or plasma VN exhibited weaker binding. Plasminogen activator inhibitor-1 (PAI-1) or heparin, but not desulfated glycosaminoglycans, interfered with binding of VN to TGF-␤, and soluble PAI-1 was able to dissociate VN-bound TGF-␤. Upon limited plasmin proteolysis of VN, only the fragments comprising the intact aminoterminal portion of VN bound to TGF-␤ as did a synthetic peptide (amino acids 43 to 62), indicating that TGF-␤ and PAI-1 share common binding site(s) on VN. Although VN did not influence TGF-␤ bioactivity for mink lung epithelial cells, TGF-␤ dose dependently inhibited both urokinase-receptor as well as ␣ v -integrin-dependent adhesion to VN. This activity of TGF-␤ was reminiscent of the antiadhesive function of PAI-1. In atherosclerotic tissue sections, staining patterns of VN and TGF-␤ indicated their colocalization. These findings describe VN as a new binding protein for TGF-␤, whereby specific functions of both factors become modulated by this interaction. (Lab Invest 2002, 82:37-46). T he extracellular matrix (ECM) is a complex structural network consisting of different collagens, sulfated proteoglycans, and adhesive glycoproteins, to which various factors are bound, which dynamically regulate cellular growth, morphogenesis, and differentiation. Among these, growth factors, proteases, and their specific inhibitors not only influence the molecular composition of the ECM but organize motility of cells and their invasiveness. The earliest reports on tethering of growth factors to the ECM included the fibroblast growth factor family (Rapraeger et al, 1991), demonstrating anchoring of these polypeptides to the polysaccharide component of heparan sulfate proteoglycans. In addition, binding of basic fibroblast growth factor (bFGF) to cell surface-associated heparin-like molecules is required for binding of the growth factor to its high-affinity receptor, thus serving as a dual receptor system for full growth factor activity (Klagsbrun and Baird, 1991;Roghani et al, 1994;Yayon et al, 1991). Other factors, such as vascular endothelial growth factor (VEGF), which act ...

show abstract

“…Therefore, plasminogen may bind either directly to the IGF-II affinity matrix or indirectly in association with IGFBP-3. Plasminogen appears not to be unique in its ability to bind IGF-II and IGFBPs, because vitronectin, a multifunctional plasma and extracellular matrix protein, has been reported also to bind IGF-II and IGFBPs directly (34). We have not tested whether the 70 -75-kDa vitronectin is present in the eluate of the IGF-II affinity matrix.…”

Section: Discussionmentioning

confidence: 99%

“…The 70-kDa protein in fraction 56 was verified as transferrin. Because it has been reported that both IGFBP-3 and IGFBP-5 bind to plasminogen migrating at a molecular mass of ϳ 92/97 kDa (16,34), fraction 53 was also tested for plasminogen immunoreactivity. This fraction contained 92-kDa plasminogen immunoreactive material with a slightly higher molecular mass than the purified standard (Fig.…”

Section: Multiple Non-igfbp Plasma Proteins Bind Igf-ii-humanmentioning

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

View full text Add to dashboard Cite

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...

show abstract

Identification of Vitronectin as a Novel Insulin-Like Growth Factor-II Binding Protein

Cited by 24 publications

References 0 publications

Comparative endocrinology of the insulin-like growth factor-binding protein

Comparative endocrinology of the insulin-like growth factor-binding protein

Molecular Interactions and Functional Interference between Vitronectin and Transforming Growth Factor-β

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

Contact Info

Product

Resources

About