Amino acid sequence of a variant pro-form of insulin-like growth factor II.

Zumstein, Peter; Lüthi, Christine; Humbel, R

doi:10.1073/pnas.82.10.3169

Cited by 106 publications

(50 citation statements)

References 24 publications

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“…We did not find pro-IGF-II proteolytically processed at Lys-88 in the trophoblasts. However, the existence of big IGF-II (1-87) in human serum (12) suggests that a previously uncharacterized enzyme-mediated cleavage at Lys-88 may exist in other cell systems.…”

Section: Discussionmentioning

confidence: 99%

“…Mature IGF-II, a 7.5-kDa peptide containing 67 amino acids, is originally synthesized as a biologically inactive pro-IGF-II peptide (156 amino acids), which subsequently undergoes regulated endoproteolytic cleavage to the mature form. In addition to mature IGF-II, two ''big'' variants, IGF-II (1-87) and IGF-II (1-104), have been identified in human and bovine serum (10)(11)(12)(13). They are 11-17 kDa in size, contain 87 or 104 amino acids, respectively, and differ in glycosylation (10)(11)(12)(13)(14).…”

mentioning

confidence: 99%

“…In addition to mature IGF-II, two ''big'' variants, IGF-II (1-87) and IGF-II (1-104), have been identified in human and bovine serum (10)(11)(12)(13). They are 11-17 kDa in size, contain 87 or 104 amino acids, respectively, and differ in glycosylation (10)(11)(12)(13)(14). It has been suggested that big IGF-II is biologically active but may have different activity in tumor cells when compared with mature IGF-II (15).…”

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confidence: 99%

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Role of pro-IGF-II processing by proprotein convertase 4 in human placental development

Qiu

Basak

Mbikay

et al. 2005

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

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Fetal growth restriction (intrauterine growth restriction, IUGR) is a leading cause of perinatal mortality. However, the causes of aberrant development of the placenta and, thus, of the fetus, are not currently known. Insulin-like growth factor II (IGF-II) has been shown to be an important regulator of fetoplacental growth. This growth factor must undergo posttranslational processing, and, thus, we hypothesized that aberrant processing of pro-IGF-II to IGF-II may be a cause of IUGR. Here, we have found that the proprotein convertase PC4 is expressed in the human placenta and that it cleaves pro-IGF-II to generate the intermediate processed form, IGF-II (1-102) and, subsequently, mature IGF-II (1-67), which are accounted for by the removal of terminal basic residues by carboxypeptidases. This processing confers the ability of IGF-II to activate invasive trophoblast cells through AKT phosphorylation, whereas inhibition of PC4 by a PC4-specific inhibitor blocks pro-IGF-II processing and reduces trophoblast cell migration, which can be partly restored by addition of mature IGF-II. Consistent with the hypothesis that IGF-II processing is implicated in IUGR, sera of patients carrying IUGR fetuses displayed elevated levels of pro-IGF-II. Thus, abnormal processing of IGF-II by PC4 may represent a previously uncharacterized mechanism involved in the pathophysiology of fetoplacental growth restriction, and elevated pro-IGF-II may be a useful clinical marker for risk of IUGR.insulin-like growth factor II ͉ intrauterine growth restriction

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Role of pro-IGF-II processing by proprotein convertase 4 in human placental development

Qiu

Basak

Mbikay

et al. 2005

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

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“…Such results can be due to two factors: incomplete hydrolysis of proteins or complicated ionization of peptides during MS-analysis of the trypsin hydrolysate. It is well-established that insulin-like growth factor II (14), like insulin, is resistant to trypsin hydrolysis under routine conditions because of covalent dimerization. Using electrophoresis and MS, insulin was found to be resistant to trypsin hydrolysis under routine conditions, and was digested only after a reduction/alkylation procedure (data not shown).…”

Section: Discussionmentioning

confidence: 99%

Proteomics of exhaled breath: methodological nuances and pitfalls

Kurova¹,

Анаев²,

Kononikhin³

et al. 2009

Clinical Chemistry and Laboratory Medicine

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Background: The analysis of exhaled breath condensate (EBC) can be an alternative to traditional endoscopic sampling of lower respiratory tract secretions. This is a simple non-invasive method of diagnosing respiratory diseases, in particular, respiratory inflammatory processes. Methods: Samples were collected with a special device-condenser (ECoScreen, VIASYS Healthcare, Germany), then treated with trypsin according to the proteomics protocol for standard protein mixtures and analyzed by nanoflow high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) with a 7-Tesla Finnigan LTQ-FT mass spectrometer (Thermo Electron, Germany). Mascot software (Matrixscience) was used for screening the database NCBInr for proteins corresponding to the peptide maps that were obtained. Results: EBCs from 17 young healthy non-smoking donors were collected. Different methods for concentrating protein were compared in order to optimize EBC preparations for proteomic analysis. The procedure that was chosen allowed identification of proteins exhaled by healthy people. The major proteins in the condensates were cytoskeletal keratins. Another 12 proteins were identified in EBC from healthy non-smokers. Some keratins were found in the ambient air and may be considered exogenous components of exhaled air. Conclusions: Knowledge of the normal proteome of exhaled breath allows one to look for biomarkers of different disease states in EBC. Proteins in ambient air can be identified in the respiratory tract and should be excluded from the analysis of the proteome of EBC. The results obtained allowed us to choose the most effective procedure of sample preparation when working with samples containing very low protein concentrations. Clin Chem Lab Med 2009;47:706-12.

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“…In normal tissue, IGF-II results from cleavage of a prepropeptide consisting of 156 amino acids. Before secretion the E-domain is removed step by step at the carboxyl terminal whereas the B-, C-, A-and D-domain belong to the fully processed mature 7.5 kDa IGF-II (21)(22)(23). The number, molecular weights and biological activities of IGF-II proforms are still unknown (24).…”

Section: Introductionmentioning

confidence: 99%

High molecular weight forms of IGF-II ('big-IGF-II') released by Wilms' tumor cells

Schmitt

Ren-Qiu²,

Torresani³

et al. 1997

European Journal of Endocrinology

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Insulin-like growth factor-II (IGF-II) is thought to play a critical role in the development of embryonic tumors such as Wilms' tumor. However, despite highly elevated IGF-II mRNA levels in tumors, IGF-II is not elevated in the serum of patients with Wilms' tumors. Recently high molecular weight forms of IGF-II ('big'-or pro-IGF-II) have been found to be produced by some tumors. In order to prove whether or not high molecular weight forms of IGF-II are produced by Wilms' tumor cells and secreted into the culture medium, we established Wilms' tumor cell lines. After column chromatography of the culture medium, IGF-II and pro-IGF-II concentrations were measured. For pro-IGF-II measurement we established a pro-IGF-II RIA using a rabbit polyclonal antiserum directed against amino acids 7-21 (E 7-21 ) of the E-domain of pro-IGF-II. Gel electrophoresis and Western blotting with anti-IGF-II antibodies revealed a band at 7.5 kDa corresponding to fully processed IGF-II and bands between 10 and 20 kDa. Using pro-IGF-II antiserum, bands between 10 and 25 kDa were detected. We conclude that in vitro cultured Wilms' tumor cells produce and release various forms of 'big IGF-II' with molecular masses between 10 and 25 kDa. It remains uncertain whether these high molecular weight forms of IGF-II represent normal precursors of IGF-II or incorrectly processed IGF-II.

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Amino acid sequence of a variant pro-form of insulin-like growth factor II.

Cited by 106 publications

References 24 publications

Role of pro-IGF-II processing by proprotein convertase 4 in human placental development

Role of pro-IGF-II processing by proprotein convertase 4 in human placental development

Proteomics of exhaled breath: methodological nuances and pitfalls

High molecular weight forms of IGF-II ('big-IGF-II') released by Wilms' tumor cells

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