Isolation and characterization of variant IGF‐1 as well as IGF‐2 from adult human brain

Carlsson-Skwirut, Christine; Jörnvall, Hans; Holmgren, Arne; Andersson, Charlotte; Bergman, Tomas; Lundquist, Gunilla; Sjögren, Benita; Sara, Vicki R.

doi:10.1016/0014-5793(86)80568-3

Cited by 98 publications

(47 citation statements)

References 15 publications

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“…We have previously reported the isolation of a potent, N-terminally truncated form of IGF-I, des-(1-3)-IGF-I, from bovine colostrum , while others have also isolated this protein from human brain (Sara et al 1986, Carlsson-Skwirut et al 1987. Hence, we were interested to know whether such a species exists in kangaroo serum.…”

Section: Discussionmentioning

confidence: 99%

Purification, amino acid sequence and characterisation of kangaroo IGF-I

Yandell

Francis²,

Wheldrake³

et al. 1998

Journal of Endocrinology

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Insulin-like growth factor-I (IGF-I) and IGF-II have been purified to homogeneity from kangaroo (Macropus fuliginosus) serum, thus this represents the first report of the purification, sequencing and characterisation of marsupial IGFs. N-Terminal protein sequencing reveals that there are six amino acid differences between kangaroo and human IGF-I. Kangaroo IGF-II has been partially sequenced and no differences were found between human and kangaroo IGF-II in the 53 residues identified. Thus the IGFs appear to be remarkably structurally conserved during mammalian radiation. In addition, in vitro characterisation of kangaroo IGF-I demonstrated that the functional properties of human, kangaroo and chicken IGF-I are very similar. In an assay measuring the ability of the proteins to stimulate protein synthesis in rat L6 myoblasts, all IGF-I proteins were found to be equally potent. The ability of all three proteins to compete for binding with radiolabelled human IGF-I to type-1 IGF receptors in L6 myoblasts and in Sminthopsis crassicaudata transformed lung fibroblasts, a marsupial cell line, was comparable. Furthermore, kangaroo and human IGF-I react equally in a human IGF-I RIA using a human reference standard, radiolabelled human IGF-I and a polyclonal antibody raised against recombinant human IGF-I. This study indicates that not only is the primary structure of eutherian and metatherian IGF-I conserved, but also the proteins appear to be functionally similar.

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Section: Discussionmentioning

confidence: 99%

Purification, amino acid sequence and characterisation of kangaroo IGF-I

Yandell

Francis²,

Wheldrake³

et al. 1998

Journal of Endocrinology

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“…The mature peptide comprises four domains, that is, the B amino-terminal domain, C and A domain and D carboxyterminal domain, of IGF-I polypeptides (25,84). In addition, two other protein products have been identified in the human brain; the tripeptide glycylprolyl-glutamate (GPE) corresponding to the NH 2 -terminal of the B domain of mature IGF-I and a truncated IGF-I form (-3N:IGF-I) that lacks the first three amino acids of the amino terminal end of mature peptide, probably due to alternate signal peptides or the combined action of some peptidases (78,85,86). Removal of the NH 2 -terminal tripeptide could be a mechanism for increasing the biological potency and availability of IGF-I, since the truncated -3N:IGF-I has less affinity for IGF-binding proteins than mature IGF-I, thus, increasing its bioactivity (78), (see Figure 1A) (see below: IGF-I Receptors and Binding Proteins).…”

Section: Igf-i Processing Secretion and Glycosylationmentioning

confidence: 99%

The Complexity of the IGF1 Gene Splicing, Posttranslational Modification and Bioactivity

Philippou

Maridaki

Pneumaticos

et al. 2014

Mol Med

100

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The insulinlike growth factor-I (IGF-I) is an important factor which regulates a variety of cellular responses in multiple biological systems. The IGF1 gene comprises a highly conserved sequence and contains six exons, which give rise to heterogeneous mRNA transcripts by a combination of multiple transcription initiation sites and alternative splicing. These multiple transcripts code for different precursor IGF-I polypeptides, namely the IGF-IEa, IGF-IEb and IGF-IEc isoforms in humans, which also undergo posttranslational modifications, such as proteolytic processing and glycosylation. IGF-I actions are mediated through its binding to several cell-membrane receptors and the IGF-I domain responsible for the receptor binding is the bioactive mature IGF-I peptide, which is derived after the posttranslational cleavage of the pro-IGF-I isoforms and the removal of their carboxy-terminal E-peptides (that is, the Ea, Eb and Ec). Interestingly, differential biological activities have been reported for the different IGF-I isoforms, or for their E-peptides, implying that IGF-I peptides other than the IGF-I ligand also possess bioactivity and, thus, both common and unique or complementary pathways exist for the IGF-I isoforms to promote biological effects. The multiple peptides derived from IGF-I and the differential expression of its various transcripts in different conditions and pathologies appear to be compatible with the distinct cellular responses observed to the different IGF-I peptides and with the concept of a complex and possibly isoform-specific IGF-I bioactivity. This concept is discussed in the present review, in the context of the broad range of modifications that this growth factor undergoes which might regulate its mechanism(s) of action.

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“…The presence of des (1-3) IGF-I in a variety of tissues and biological fluids [7][8][9][10], the demonstration of enhanced biological activity of this variant in both in vitro and in vivo assays [4,5] and the observation suggesting that the proteolytic activity which generates this IGF-I variant is inversely regulated by growth hormone [12] suggest that the generation of des (1-3) IGF-I is unlikely to represent an unimportant degradation pathway. Furthermore, although des (1-3) IGF-I has not been detected in plasma, it is unlikely to be an artifact resulting from tissue disruption during extraction since it is also present in breast milk and possibly in urine [10,13].…”

Section: Discussionmentioning

confidence: 99%

“…N-terminal truncated variants of IGF-I and IGF-II, des (1-3) IGF-I [4,5] and des (1-6) IGF-II [6], are biologically more potent than intact IGF-I and IGF-II, respectively, because these variants have reduced affinity for the IGFBPs but their affinity for the type-I IGF receptor is similar to that of intact IGF. Des (1-3) IGF-I has been identified in a variety of tissue extracts and biological fluids [7][8][9][10], whereas des (1-6) IGF-II has not yet been found. Our recent demonstration of a protease in the rat serum which is capable of generating des (1-3) IGF-I from IGF-I [11] suggests that N-terminal truncation of IGFs regulates the bioavailability of these growth factors.…”

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confidence: 99%