A Novel Binding Site for the Human Insulin-like Growth Factor-II (IGF-II)/Mannose 6-Phosphate Receptor on IGF-II

Delaine, Carlie; Alvino, Clair L.; McNeil, Kerrie A.; Mulhern, Terrence D.; Gauguin, Lisbeth; Meyts, Pierre De; Jones, E Y; Brown, James; Wallace, John C.; Forbes, Briony E.

doi:10.1074/jbc.m700531200

Cited by 35 publications

(55 citation statements)

References 38 publications

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“…Analog Production and Receptor and IGFBP Binding AssaysProduction of IGF-II analogs and purification and binding assays using IGF-1R, IR-A, and domains 10 -13 of the IGF2R are described in Delaine et al (12). IGFBP-2 binding affinities were derived from BIAcore analyses performed as described by Carrick et al (14).…”

Section: Methodsmentioning

confidence: 99%

Insulin-like Growth Factor-II (IGF-II) and IGF-II Analogs with Enhanced Insulin Receptor-a Binding Affinity Promote Neural Stem Cell Expansion

Ziegler

Chidambaram

Forbes

et al. 2014

Journal of Biological Chemistry

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Section: Methodsmentioning

confidence: 99%

Insulin-like Growth Factor-II (IGF-II) and IGF-II Analogs with Enhanced Insulin Receptor-a Binding Affinity Promote Neural Stem Cell Expansion

Ziegler

Chidambaram

Forbes

et al. 2014

Journal of Biological Chemistry

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“…Correct folding of the analogues was tested by recording far UV circular dichroism (CD) spectra. This method has been described previously (34).…”

Section: Methodsmentioning

confidence: 99%

“…The soluble receptor assay was performed as described in Delaine et al (34). Briefly, P6 IGF-IR cells were serum-starved 4 h before lysis with lysis buffer (20 mM HEPES, 150 mM NaCl, 1.5 mM MgCl 2 , 10% (v/v) glycerol, 1% (v/v) Triton X-100, 1 mM EGTA, and 1 mM phenylmethylsulfonyl fluoride, pH 7.5) for 1 h at 4°C.…”

Section: Methodsmentioning

confidence: 99%

Alanine Scanning of a Putative Receptor Binding Surface of Insulin-like Growth Factor-I

Gauguin¹,

Delaine

Alvino

et al. 2008

Journal of Biological Chemistry

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Current evidence supports a binding model in which the insulin molecule contains two binding surfaces, site 1 and site 2, which contact the two halves of the insulin receptor. The interaction of these two surfaces with the insulin receptor results in a high affinity cross-linking of the two receptor ␣ subunits and leads to receptor activation. Evidence suggests that insulin-like growth factor-I (IGF-I) may activate the IGF-I receptor in a similar mode. So far IGF-I residues structurally corresponding to the residues of the insulin site 1 together with residues in the C-domain of IGF-I have been found to be important for binding of IGF-I to the IGF-I receptor (e.g. results in a significant reduction in IGF-I receptor binding affinity, whereas alanine substitution at position 53 had no effect on IGF-I receptor binding. The multiple substitutions resulted in a 33-100-fold reduction in IGF-I receptor binding affinity. These data suggest that IGF-I, in addition to the C-domain, uses surfaces similar to those of insulin in contacting its cognate receptor, although the relative contribution of the side chains of homologous residues varies. IGF-I2 is a single chain polypeptide that plays an important role in regulating growth and development (1, 2). IGF-I consists of 70 amino acid residues arranged in four domains. The A and B domains are homologous to the A and B chains of insulin (Fig. 1), whereas the C-domain connecting the A-and B-domain and the D-domain extending from the C-terminal end of the A-domain are only present in IGF-I (3-5). The three-dimensional structures of insulin and IGF-I are also very similar. The B-domain of the two molecules is arranged in a central ␣-helix including residues 8 -17 (B9 -B19) (insulin residues in parentheses), and the A-domain contains two anti-parallel ␣-helices including residues 43-48 (A1-A8) and residues 54 -60 (A13-A20) (4, 6, 7).The insulin receptor family consists of the insulin receptor (IR), insulin-like growth factor-I receptor (IGF-IR) and the insulin-receptor-related receptor, all of which are receptortyrosine kinases. The members of the insulin receptor family consist of two receptor halves, each comprising an extracellular ␣-subunit and a transmembrane ␤-subunit, linked by a disulfide bridge. The receptor exists as a dimer when no ligand is bound, making an ␣2␤2 receptor held together by disulfide bridges between the two ␣-subunits. The IR and the IGF-IR have sequence similarities varying from 41 to 84% depending on which regions are being compared. The overall structure of the L1-Cys-rich-L2 domains of the two receptors have been shown by x-ray crystallography to be similar (8 -11).Numerous studies indicate that the IR and IGF-IR contains two separate binding sites for the ligand; however, only one ligand binds and activates the ␣2␤2 receptor dimer. Insulin is believed to interact with the receptor using two binding surfaces, which cross-link the two receptor halves. This cross-

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“…IGF2 has been shown to promote bovine granulosa cell proliferation and steroidogenesis by binding to IGF1R (Spicer & Aad 2007). In contrast, IGF2 binding to IGF2R results in the inactivation of IGF2 (Delaine et al 2007). In this study, expression of IGF2R did not change significantly with follicle size but was higher during the transitional period than during the ovulatory period.…”

Section: Discussionmentioning

confidence: 54%

“…In addition to IGF1, IGF2 is found in equine follicular fluid and can bind and activate IGF1R (Spicer & Aad 2007). IGF2 activity is negatively regulated by IGF2 binding to a second receptor, IGF2R (Delaine et al 2007). Follicular availability of IGF1 is thought to be regulated primarily by IGF-binding proteins (IGFBPs) which render IGF1 inactive (Mazerbourg et al 2003).…”

Section: Introductionmentioning

confidence: 99%

Seasonal effects on the response of ovarian follicles to IGF1 in mares

Doyle

Hogg²,

Watson³

et al. 2008

Reproduction

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The response of follicles to IGF1 was compared between the transition into the ovulatory season (transitional period) and the ovulatory season (ovulatory period) in eight mares using a cross-over experimental design within periods. Granulosa cells were collected from follicles 15-24 or 25-34 mm and expression of IGF1R, IGF2R, FSHR, LHCGR and PAPPA was determined by qPCR. In addition, 10 mg IGF1 or vehicle were injected into the largest follicle (transitional period) or the second largest follicle (ovulatory period) of a follicular wave before the beginning of diameter deviation between the two largest follicles (mean diameters at injection 19.2 and 20.0 mm during transitional and ovulatory periods respectively). Follicular fluid was collected 24 h after injection for determination of free IGF1, IGFBP, inhibin A and oestradiol levels. Granulosa cells from follicles 25-34 mm, but not follicles 15-24 mm, expressed higher levels of IGF1R (PZ0.01), FSHR (P!0.007) and LHCGR (PZ0.09) during the ovulatory period than during the transitional period, whereas IGF2R expression was higher in transitional than ovulatory follicles (PZ0.06). Follicular IGFBP2 levels were not different (PO0.1) between periods and treatments, whereas IGFBP5 levels were higher (P!0.05) during the ovulatory period. Finally, IGF1 injection before the beginning of deviation induced an approximately twofold increase (PZ0.01) in follicular inhibin A levels during each period and did not affect oestradiol (PO0.1). These results suggest that, as during ovulatory waves, equine follicles during transitional waves are responsive to IGF1 before the beginning of deviation and that, therefore, inadequate IGF1 responsiveness before deviation may not underlie the deficient development of dominant follicles during transition. Reproduction (2008) 136 589-598

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A Novel Binding Site for the Human Insulin-like Growth Factor-II (IGF-II)/Mannose 6-Phosphate Receptor on IGF-II

Cited by 35 publications

References 38 publications

Insulin-like Growth Factor-II (IGF-II) and IGF-II Analogs with Enhanced Insulin Receptor-a Binding Affinity Promote Neural Stem Cell Expansion

Insulin-like Growth Factor-II (IGF-II) and IGF-II Analogs with Enhanced Insulin Receptor-a Binding Affinity Promote Neural Stem Cell Expansion

Alanine Scanning of a Putative Receptor Binding Surface of Insulin-like Growth Factor-I

Seasonal effects on the response of ovarian follicles to IGF1 in mares

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