Insulin‐like growth factors I and II

Humbel, R

doi:10.1111/j.1432-1033.1990.tb15595.x

Cited by 760 publications

(502 citation statements)

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“…They share 62% homology in amino acids sequence and there is 40% homology between the IGFs and proinsulin 15,16 . As their name suggests they are growth factors with growth promoting properties in numerous tissues and are present in high concentrations in serum.…”

Section: Igf-1 Andmentioning

confidence: 99%

The GH–IGF-I axis and breast cancer

Laban

Bustin

Jenkins

2003

Trends in Endocrinology & Metabolism

109

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Section: Igf-1 Andmentioning

confidence: 99%

The GH–IGF-I axis and breast cancer

Laban

Bustin

Jenkins

2003

Trends in Endocrinology & Metabolism

109

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“…Cells were washed again and incubated with PBS containing diaminobenzidine gated streptavidin from Zymed Laboratories (San Francisco, CA). The monoclonal antibodies ED1 and ED2 were supplied (0.5 mg/mL), H 2 Animals. Adult male Wistar rats (2 to 3 months old; body minutes, washed and counterstained in Meyer's hemalum.…”

mentioning

confidence: 99%

Synthesis of insulinlike growth factor binding proteins and of the acid-labile subunit in primary cultures of rat hepatocytes, of Kupffer cells, and in cocultures: Regulation by insulin, insulinlike growth factor, and growth hormone

Scharf¹,

Ramadori²,

Braulke³

et al. 1996

Hepatology

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The adult liver is the main source of circulatingThe insulinlike growth factors (IGF-I and IGF-II) are insulinlike growth factors (IGFs ) and their serum circulating peptides with structural homology to proinbinding proteins (IGFBPs) including the acid-labile sulin. 1,2 They are known to participate in the regulation subunit (ALS), a component of the ternary binding of growth, metabolism, and cellular differentiation. 3 protein complex. Within the liver, the biosynthesis of The adult liver has been recognized as the major site individual proteins has been attributed to different of IGF biosynthesis. 4,5 cell populations, e.g., that of ALS to hepatocytes andIn serum, IGFs bind with high affinity to specific that of IGFBP-3 to nonparenchymal cells. Ligand and binding proteins. So far, six distinct binding proteins immunoblotting as well as Northern blotting analyses (named IGFBP-1 to -6) have been identified. 6 In the 3, and of the acid-labile subunit (ALS). 7,8 Formation ofsynthesis of IGFBP-1, -2, and -4 was observed; insulin and IGF-I decreased that of IGFBP-1, and -2 while in-this ternary complex is believed to prolong half-life of creasing that of IGFBP-4. KCs synthesized IGFBP-2, IGFs in systemic circulation 9 and to prevent acute insuand -3, insulin and IGF-I showing no effect. In cocul-linlike actions of these peptides, i.e., hypoglycemia. In tures, however, synthesis of IGFBP-3 was stimulated addition, IGFs form binary complexes with other by insulin and IGF-I. By immunocytochemistry IGFBPs (e.g., IGFBP-1, -2, and -4) of 31 to 40 kd that IGFBP-3 biosynthesis was localized to KCs exclu-are capable of crossing capillary walls and facilitating sively. When pore membranes were used for separa-IGF transport to target tissues. 10 tion of hepatocytes and KCs in coculture, this in-The biosynthesis of serum IGFBPs has been localized sulin-stimulatory action on IGFBP-3 synthesis was to the liver, too. 11 Recently, several studies in rats have size this glycosylated 82-to 88-kd protein. 16,17 Regulation of biosynthesis of individual IGFBPs and of ALS is not uniform and apparently linked to condi- Before the addition of hormones, cultures and cocultures of rat liver cells specific activity of approximately 60 to 80 mCi/mg. Porcine insulin, dexamethasone, and glucose oxidase were obtained were washed with the M-199 medium supplemented with 0.2% (wt/vol) BSA and then incubated in the culture medium from Sigma Chemical Co. (Deisenhofen, Germany). Human GH was kindly donated by Nordisk (Mainz, Germany). En-at 37ЊC for 1 hour. The medium was then replaced by fresh medium supplemented with 0.2% (wt/vol) BSA, and the cells zymes, fetal calf serum (FCS), and M-199 medium were purchased from Boehringer Mannheim (Mannheim, Germany). were incubated in the presence or absence of insulin, IGF-I, and GH in concentrations ranging from 0.1 to 100 nmol/L Bovine serum albumin (BSA), glucagon, and antibiotics were from Serva Feinbiochemica Gmbtt & Co. KG (Heidelberg, each for 36 hours.Immunocytochemistry. For immunocytochemical analys...

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“…The expression plasmids encoding Expression, Purification, and Identification of [1][2][3][4][5][6][7][8][9]PIP, [1][2][3][4]PIP, [1][2][3][4][5][6][7][8][9][10]Mini-IGF-1, and [1][2][3][4][5]…”

Section: Methodsmentioning

confidence: 99%

“…, and pVT102-U/RMFL- [1][2][3][4][5]mini-IGF-1 were transformed into S. cereVisiae cells of strain XV700-6B (leu2 ura3 pep4). The transformed yeast cells were cultured in a 16-L fermenter and the secreted target protein was purified from the medium in four steps (16,19).…”

Section: Methodsmentioning

confidence: 99%

“…Its three-dimensional structure has been well defined by X-ray crystallography (1) and NMR (2-4) since the 1970s. Insulin-like growth factor-1 (IGF-1) 1 is a 70-residue single-chain globular protein composed of B-, C-, A-, and D-domains from the N-terminus to the C-terminus (5). Its B-and A-domains are homologous to the B-and A-chains of insulin, respectively; its 12-residue C-domain is analogous to the C-peptide of proinsulin, but they share no homology; its C-terminal 8-residue D-domain has no counterpart in insulin.…”

mentioning

confidence: 99%

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Sequences of B-Chain/Domain 1−10/1−9 of Insulin and Insulin-like Growth Factor 1 Determine Their Different Folding Behavior

et al. 2004

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Although insulin and insulin-like growth factor-1 (IGF-1) belong to one family, insulin folds into one thermodynamically stable structure, while IGF-1-folds into two thermodynamically stable structures (native and swap forms). We have demonstrated previously that the bifurcating folding behavior of IGF-1 is mainly controlled by its B-domain. To further elucidate which parts of the sequences determine their different folding behavior, by exchanging the N-terminal sequences of mini-IGF-1 and recombinant porcine insulin precursor (PIP), we prepared four peptide models: [1-9]PIP, [1-10]mini-IGF-1, [1-4]PIP, and [1-5]mini-IGF-1 by means of protein engineering, and their disulfide rearrangement, V8 digestion, circular dichroic spectra, disulfide stability, and in vitro refolding were investigated. Among them only [1-9]-PIP, like mini-IGF-1/IGF-1, was expressed in yeast as two isomers: isomer 1 (corresponding to swap IGF-1) and isomer 2 (corresponding to native IGF-1), which are supported by the experimental results of disulfide rearrangements, peptide mapping of V8 endoprotenase digests, circular dichroic analysis, in vitro refolding, and disulfide stability analysis. The other peptide models, [1-10]mini-IGF-1, [1-4]PIP, and [1-5]mini-IGF-1, fold into one stable structure as PIP does, which indicates that sequence 1-4 of mini-IGF-1 is important for the folding behavior of mini-IGF-1/IGF-1 but not sufficient to lead to a bifurcating folding. The results demonstrated that the folding information, by which mini-IGF-1/IGF-1-folds into two thermodynamically structures, is encoded/written in its sequence 1-9, while sequences 1-10 of B chain in insulin/PIP play an important role in the guide of its unique disulfide pairing during the folding process.Insulin is a structurally and functionally well-characterized small globular protein with A-and B-chains linked by three disulfides. Its three-dimensional structure has been well defined by X-ray crystallography (1) and NMR (2-4) since the 1970s. Insulin-like growth factor-1 (IGF-1) 1 is a 70-residue single-chain globular protein composed of B-, C-, A-, and D-domains from the N-terminus to the C-terminus (5). Its B-and A-domains are homologous to the B-and A-chains of insulin, respectively; its 12-residue C-domain is analogous to the C-peptide of proinsulin, but they share no homology; its C-terminal 8-residue D-domain has no counterpart in insulin. The three-dimensional structure of IGF-1 has also been well-defined by X-ray crystallography (6, 7) and NMR (8, 9). Insulin and IGF-1 belong to the same superfamily. They have a common structural motif (10, 11) and share homologous sequence, similar three-dimensional structure (1,6,7), and a common ancestor (12,13). Both mainly consist of three R-helical segments (A2-A8, A13-A19, and B9-B19 in insulin; 8-18, 42-49, and 54-61 in IGF-1) in the A-and B-chains/domains; the three R-helical segments are stabilized by three identical disulfides (A6-A11, A7-B7, and A20-B19 in insulin; 47-52, 6-48, and 18-61 in IGF-1); and when IGF-1...

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Insulin‐like growth factors I and II

Cited by 760 publications

References 318 publications

The GH–IGF-I axis and breast cancer

The GH–IGF-I axis and breast cancer

Synthesis of insulinlike growth factor binding proteins and of the acid-labile subunit in primary cultures of rat hepatocytes, of Kupffer cells, and in cocultures: Regulation by insulin, insulinlike growth factor, and growth hormone

Sequences of B-Chain/Domain 1−10/1−9 of Insulin and Insulin-like Growth Factor 1 Determine Their Different Folding Behavior

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