Identification of the amniotic fluid insulin-like growth factor binding protein-1 phosphorylation sites and propensity to proteolysis of the isoforms.

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Citation

Dolcini L, Sala A, Campagnoli M, Labo S, Valli M, Visai L, Minchiotti L, Monaco HL, Galliano M

Identification of the amniotic fluid insulin-like growth factor binding protein-1 phosphorylation sites and propensity to proteolysis of the isoforms.

FEBS J. 2009 Oct;276(20):6033-46. doi: 10.1111/j.1742-4658.2009.07318.x. Epub 2009 Sep 17.

PubMed ID
19765076 [ View in PubMed
]
Abstract

Insulin-like growth factor binding protein-1 (IGFBP-1) is the major secreted protein of human decidual cells during gestation and, as a modulator of insulin-like growth factors or by independent mechanisms, regulates embryonic implantation and growth. The protein is phosphorylated and this post-translational modification is regulated in pregnancy and represents an important determinant of its biological activity. We have isolated, from human normal amniotic fluid collected in the weeks 16-18, the intact nonphosphorylated IGFBP-1 and five electrophoretically distinct phosphoisoforms and have determined their in vivo phosphorylation state. The unmodified protein was the most abundant component and mono-, bi-, tri- and tetraphosphorylated forms were present in decreasing amounts. The phosphorylation sites of IGFBP-1 were identified by liquid chromatography-tandem mass spectrometry analysis of the peptides generated with trypsin, chymotrypsin and Staphylococcus aureus V8 protease. Five serines were found to be phosphorylated and, of these, four are localized in the central, weakly conserved, region, at positions 95, 98, 101 and 119, whereas one, Ser169, is in the C-terminal domain. The post-translational modification predominantly involves the hydrophilic stretch of amino acids representing a potential PEST sequence (proline, glutamic acid, serine, threonine) and our results show that the phosphorylation state influences the propensity of IGFBP-1 to proteolysis.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Insulin-like growth factor-binding protein 1P08833Details