Placental Protein 12 Is a Decidual Protein that Binds Somatomedin and Has an Identical N-Terminal Amino Acid Sequence with Sdmatomedin-Binding Protein from Human Amhiotic Fluid*

Koistinen, Riitta; Kalkkinen, Nisse; Huhtala, Marja-Liisa; Seppälä, Markku; Bohn, H.; Rutanen, Eeva‐Marja

doi:10.1210/endo-118-4-1375

Cited by 220 publications

(51 citation statements)

References 16 publications

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“…Since the elucidation of the identity of the first IGFBP in 1986 (Koistinen et al 1986), we now know that the IGFBP system is extremely complex, involving several IGFBPs, IGFBP proteases, inhibitors and activators of IGFBP proteases. Furthermore, we have made considerable progress towards understanding the functions of IGFBPs, revealing that they are unusually pleotrophic molecules, with functions ranging from traditional carrier proteins to growth factors independent of IGFs.…”

Section: Discussionmentioning

confidence: 99%

IGF-binding proteins are multifunctional and act via IGF-dependent and -independent mechanisms

Mohan

Baylink²

2002

Journal of Endocrinology

387

300

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Traditionally, binding proteins are known to regulate the activity of ligands by prolonging their half-life, and insulin-like growth factor (IGF)-binding proteins (IGFBPs) are no exception to this. The IGFBP family contains six high-affinity members with variable functions and mechanisms of actions. In addition to functioning as simple carrier proteins, IGFBPs in serum function to regulate the endocrine actions of IGFs by regulating the amount of IGF available to bind to signaling IGF-I receptors, whereas locally produced IGFBPs act as autocrine/paracrine regulators of IGF action. Furthermore, recent in vitro and in vivo findings that IGFBPs function independently of the IGFs as growth modulators are particularly exciting. Regarding the role of IGFBPs as ligand-independent growth modulators, our recent data that IGFBP-5 stimulates markers of bone formation in osteoblasts lacking functional IGFs provide evidence that IGFBP-5 itself is a growth factor that can act independently of IGFs to regulate bone formation. In terms of the mechanism by which certain IGFBPs mediate their effects in a ligand-independent manner, the binding of IGFBP to its putative receptor on the cell membrane may stimulate the signaling pathway independent of an IGF receptor, to mediate the effects of IGFBPs in certain target cell types. IGFBPs may also exert IGF-independent effects by transcriptional activation of genes by IGFBPs transported into the nucleus via their nuclear localization signal. In conclusion, IGFBPs are unusually pleotrophic molecules with functions ranging from the traditional role of prolonging the half-life of the IGFs to functioning as growth factors independent of the IGFs. In this regard, it was surprising to find that the human genome contains only about 35 000 genes. One mechanism to account for such complexity with a relatively small number of genes is strikingly illustrated by the multifunctional IGFBP class of proteins.

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Section: Discussionmentioning

confidence: 99%

IGF-binding proteins are multifunctional and act via IGF-dependent and -independent mechanisms

Mohan

Baylink²

2002

Journal of Endocrinology

387

300

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“…Hence they are likely to belong to the family of small molecular weight BPs which are growth hormone independent (Hardouin et al, 1987;Hintz et al, 1981;Hall et al, 1988). Proteins of this group have been termed placental protein 12 (ppl2) (Koishnen et al, 1986), BP28 (Baxter et al, 1987), IGFBP-25 (Lee et al, 1988), IBP-1 (Brinkman et al, 1988) and pregnancy associated endometrial-y-globulin (Bell & Keyte, 1988).…”

Section: Detection Of Immunoreactive Igf-i In Cell Conditioned Mediamentioning

confidence: 99%

Production of immunoreactive insulin-like growth factor-I (IGF-I) and IGF-I binding proteins by human lung tumours

Reeve

Payne²,

Bleehen³

1990

Br J Cancer

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Summary The production of insulin-like growth factor I (IGF-I) and IGF-I binding proteins (BPs) by human lung tumour cell lines in vitro has been examined and the levels of these substances in the serum of lung cancer patients investigated. While small cell lung cancer (SCLC) cell lines secreted both IGF-I and BPs, non-small cell lung cancer (NSCLC) cell lines secreted BPs only. No evidence of increased serum IGF-I levels was obtained in a cohort of 52 lung cancer patients having SCLC and NSCLC histologies. In contrast, serum levels of low molecular weight BPs were markedly elevated in the majority of lung cancer patients.The detection of elevated immunoreactive insulin-like growth factor-I (IGF-I) in human lung tumours (Minuto et al., 1986;Macaulay et al., 1988a) Healthy adult male and female non-smokers (n = 32), and male and female normal smokers (n = 31) were included in the study as controls. The age range for controls was 23-81 years and for lung cancer patients 39-79 years.Pre-treatment serum samples were prepared immediately after collection and stored at -70'C before assay. IGF-I determinationsA radioimmunoassay (RIA) kit (Amersham International, Aylesbury, UK) and a somatomedin C (SM-C) immunoradiometric (IRMA) kit (Immunodiagnostics Ltd, Tyne and Wear, UK) were used for the quantitative measurement of IGF-I in conditioned media and serum samples. Recombinant human IGF-I was used as standards in both assays. The rabbit antiserum used in the competitive RIA was raised against a recombinant analogue of IGF-I, shows 100% cross-reactivity with human IGF-I and 0.5% crossreactivity with human IGF-II. Fifty per cent displacement of tracer occurs with insulin at 2,000 ftunits ml-' (normal range of insulin in fasting individuals is 4-30 gunits ml-' in serum). Phase separation was achieved using Amerlex-M donkey anti-rabbit reagent (Amersham UK). Assay sensitivity is 100pg per tube.The non-competitive SM-C IRMA employed a two site immunoradiometric assay. Briefly standards/samples were incubated simultaneously with a mouse monoclonal anti-SM-C lgG immobilised on the inside walls of test tubes and a '25I-labelled mouse monoclonal antibody directed against a second IGF-I epitope. Unbound materials were then removed by decanting and washing the tubes. The antisera show 3% cross-reactivity with IGF-II and did not cross-react at all with insulin or pro-insulin. The lowest detectable level of SM-C that could be distinguished from the zero standard was 8 mU ml' at the 95% confidence limit.To separate binding protein from IGF-I, serum samples and cell conditioned media were extracted by incubation in 50 of acid extraction solution (supplied by Immunodiagnostics Ltd) for 10min at room temperature. Neutralising solution (500pl) (supplied by Immunodiagnostics Ltd) was then added to each sample. This extraction procedure yields aproximately 100% recovery of SM-C in patient samples. The neutralised, extracted conditioned media and serum samples, and unextracted serum samples were then used in the Amersham RIA and the IRMA.

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“…At least two forms, IGF-BP I and IGF-BP II, have been identified. The N-terminal sequences of IGF-BP I derived from several human sources (amniotic fluid, placental membranes, decidua, and HEP G2 hepatoma cells) are identical (5)(6)(7)(8). The cloning and complete sequence of cDNA encoding IGF-BP I from HEP G2, human uterus, and human placental cDNA libraries have been recently reported (9)(10)(11)(12).…”

mentioning

confidence: 99%

Isolation of an inhibitory insulin-like growth factor (IGF) binding protein from bone cell-conditioned medium: a potential local regulator of IGF action.

Mohan

Bautista

Wergedal

et al. 1989

Proc. Natl. Acad. Sci. U.S.A.

331

127

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Inhibitory insulin-like growth factor binding protein (In-IGF-BP) has been purified to homogeneity from medium conditioned by TE89 human osteosarcoma cells by two different methods using Sephadex G-100 gel filtration, FPLC Mono Q ion-exchange, HPLC C4 reverse-phase, HPLC CN reverse-phase, and affinity chromatographies. In-IGF-BP thus purified appeared to be homogeneous and unique by the following criteria. (i) N-terminal sequence analysis yielded a unique sequence (Asp-Glu-Ala-Ile-His-Cys-Pro-Pro-GluSer-Glu-Ala-Lys-Leu-Ala). (i) Amino acid composition of In-IGF-BP revealed marked differences with the amino acid compositions of other known BPs. (iii) In-IGF-BP exhibited a single band with a molecular mass of 25 kDa under reducing conditions on sodium dodecyl sulfate/polyacrylamide gels.

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Placental Protein 12 Is a Decidual Protein that Binds Somatomedin and Has an Identical N-Terminal Amino Acid Sequence with Sdmatomedin-Binding Protein from Human Amhiotic Fluid*

Cited by 220 publications

References 16 publications

IGF-binding proteins are multifunctional and act via IGF-dependent and -independent mechanisms

IGF-binding proteins are multifunctional and act via IGF-dependent and -independent mechanisms

Production of immunoreactive insulin-like growth factor-I (IGF-I) and IGF-I binding proteins by human lung tumours

Isolation of an inhibitory insulin-like growth factor (IGF) binding protein from bone cell-conditioned medium: a potential local regulator of IGF action.

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