The design, expression, and characterization of human insulin-like growth factor II (IGF-II) mutants specific for either the IGF-II/cation-independent mannose 6-phosphate receptor or IGF-I receptor.

Sakano, Katsu-ichi; Enjoh, T.; Numata, Fumio; Fujiwara, Hiroyuki; Marumoto, Yasumasa; Higashihashi, N.; Sato, Yasuomi D.; Perdue, James F.; Fujita‐Yamaguchi, Yoko

doi:10.1016/s0021-9258(18)54755-4

Cited by 138 publications

(12 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For analysis of the intragenic location of substitutions into Igf2, we used sequences from nine species of mammal : Bos taurus (Z68151), a ia porcellus (S59899), Equus caballus (U11241), Homo sapiens (M29645), Mustela ison (S63459), Mus musculus (M36331 and M36332), O is aries (M89788), Rattus nor egicus (M29879 and M29880) and Sus scrofa (X56094). The location of binding sites has been described previously (Sakano et al 1991 ;Hashimoto et al 1995). The sequences were analysed using PROTPARS and DNAPARS from PHYLIP (Felsenstein 1995), which provides phylogenetic independent assessment of the position of substitutions.…”

Section: Methodsmentioning

confidence: 99%

Molecular evolution of imprinted genes: no evidence for antagonistic coevolution

McVean

Hurst

1997

Proc. R. Soc. Lond. B

View full text Add to dashboard Cite

SUMMARYGenomically imprinted genes are those for which expression is dependent on the sex of the parent from which they are derived. Numerous theories have been proposed for the evolution of genomic imprinting ; one theory is that it is an intra-individual manifestation of classical parent-offspring conflict. This theory is unique in predicting that an arms race may develop between maternally and paternally derived genes for the control of foetal growth demands. Such antagonistic coevolution may be mediated through changes in the structure of the proteins concerned. Comparable coevolution is the most likely explanation for the rapid changes seen in antigenic components of parasites and antigen recognition components of immune systems. We have examined the evolution of insulin-like growth factor (Igf2) and its antagonistic receptor (Igf2r) and find that, in contrast to immune genes, at the sites of mutual binding they are highly conserved. In addition, we have analysed the rate of molecular evolution of seven imprinted genes (including Igf2 and Igf2r), sequenced in both mouse and rat, and find that this is the same as that of nonimprinted receptors and significantly lower than that of immune genes (controlling for differences in mutation rate). Contrary to the expectations of the conflict hypothesis, we hence find no evidence for antagonistic coevolution of imprinted genes mediated by changes in sequence.

show abstract

Section: Methodsmentioning

confidence: 99%

Molecular evolution of imprinted genes: no evidence for antagonistic coevolution

McVean

Hurst

1997

Proc. R. Soc. Lond. B

View full text Add to dashboard Cite

show abstract

“…The expression in conventional bacterial or yeast expression systems results in the production of biologically inactive proteins that have to be refolded to the proper conformation [9]. The same problem persists in expression systems with insect cells [10]. Nevertheless, if IGF II is expressed as a chimaera with the signal peptide and the N-terminal sequence of the insulin-like insect hormone bombyxin, a properly folded, biologically active molecule (BOMIGF) can be produced in a secreted form [11].…”

Section: Introductionmentioning

confidence: 99%

Preparation of a recombinant chimaera of insulin-like growth factor II and interleukin 3 with high proliferative potency for haemopoietic cells

DiFalco

Congote

1997

Biochemical Journal

View full text Add to dashboard Cite

We have found that a slightly modified insulin-like growth factor II (IGF II) consisting of a chimaera of bombyxin and human IGF II (BOMIGF) is properly secreted in insect cells by using the baculovirus expression system. Human interleukin 3 (IL-3) was attached to the C-terminal amino acid residue of BOMIGF with peptide linkers containing five or twelve residues. Only the chimaera with the 12-residue linker had biological activities of both IGF II and IL-3. The chimaera had a significantly higher mitogenic activity than IL-3 in cell cultures of the human haemopoietic cell line TF-1 and its effect could be observed even at femtomolar concentrations. It was also able to stimulate thymidine incorporation in IGF II-dependent bovine fetal erythroid cells. The chimaera significantly increased the number of macroscopic haemopoietic colonies in cultures of human peripheral blood in comparison with IL-3 or mixtures of IL-3 and BOMIGF in vitro. Subcutaneous injection of a BOMIGF-mouse IL-3 chimaera in normal C57BL/6 mice resulted in a significant increase of the number of spleen stem cells producing macroscopic haemopoietic colonies. This new system for the biosynthesis of IGF-cytokine fusion proteins in insect cells might prove advantageous for the low-cost and high-yield production of molecules with complementary or synergistic biological activities.

show abstract

“…Although the receptor-binding surfaces of insulin and both IGFs have a similar side chain pattern, ,,, it is assumed that each molecule uses a slightly different IR-A, IR-B, or IGF-1R binding mechanism, triggering subsequently specific signaling cascades. ,, Moreover, the differential binding of insulin and IGFs to so-called hybrid receptors (receptor heterodimers formed by IR-A/B and IR-A/IGF-1R αβ subunits) brings even more complexity to the IGF/insulin system. , …”

mentioning

confidence: 99%

Insulin–Insulin-like Growth Factors Hybrids as Molecular Probes of Hormone:Receptor Binding Specificity

et al. 2016

View full text Add to dashboard Cite

Insulin, insulin-like growth factors 1 and 2 (IGF-1 and -2, respectively), and their receptors (IR and IGF-1R) are the key elements of a complex hormonal system that is essential for the development and functioning of humans. The C and D domains of IGFs (absent in insulin) likely play important roles in the differential binding of IGF-1 and -2 to IGF-1R and to the isoforms of IR (IR-A and IR-B) and specific activation of these receptors. Here, we attempted to probe the impact of IGF-1 and IGF-2 D domains (DI and DII, respectively) and the IGF-2 C domain (CII) on the receptor specificity of these hormones. For this, we made two types of insulin hybrid analogues: (i) with the C-terminus of the insulin A chain extended by the amino acids from the DI and DII domains and (ii) with the C-terminus of the insulin B chain extended by some amino acids derived from the CII domain. The receptor binding affinities of these analogues and their receptor autophosphorylation potentials were characterized. Our results indicate that the DI domain has a more negative impact than the DII domain does on binding to IR, and that the DI domain Pro-Leu-Lys residues are important factors for a different IR-A versus IR-B binding affinity of IGF-1. We also showed that the additions of amino acids that partially "mimic" the CII domain, to the C-terminus of the insulin B chain, change the binding and autophosphorylation specificity of insulin in favor of the "metabolic" IR-B isoform. This opens new venues for rational enhancement of insulin IR-B specificity by modifications beyond the C-terminus of its B chain.

show abstract

The design, expression, and characterization of human insulin-like growth factor II (IGF-II) mutants specific for either the IGF-II/cation-independent mannose 6-phosphate receptor or IGF-I receptor.

Cited by 138 publications

References 34 publications

Molecular evolution of imprinted genes: no evidence for antagonistic coevolution

Molecular evolution of imprinted genes: no evidence for antagonistic coevolution

Preparation of a recombinant chimaera of insulin-like growth factor II and interleukin 3 with high proliferative potency for haemopoietic cells

Insulin–Insulin-like Growth Factors Hybrids as Molecular Probes of Hormone:Receptor Binding Specificity

Contact Info

Product

Resources

About