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Phosphorylation of proteins during human myometrial contractions: a phosphoproteomic approach

Research output: Contribution to journalArticle

  • Claire Hudson
  • Andres Lopez Bernal
Original languageEnglish
Pages (from-to)1393-1399
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume482
Issue number4
Early online date9 Dec 2016
DOIs
DateAccepted/In press - 7 Dec 2016
DateE-pub ahead of print - 9 Dec 2016
DatePublished (current) - 22 Jan 2017

Abstract

Phasic myometrial contractility is a key component of human parturition and the contractions are driven by reversible phosphorylation of myosin light chains catalyzed by the calcium (Ca2+)-dependent enzyme myosin light chain kinase (MYLK). Other yet unknown phosphorylation or de-phosphorylation events may contribute to myometrial contraction and relaxation. In this study we have performed a global phosphoproteomic analysis of human myometrial tissue using tandem mass tagging to detect changes in the phosphorylation status of individual myometrial proteins during spontaneous and oxytocin-driven phasic contractions. We were able to detect 22 individual phosphopeptides whose relative ratio changed (fold > 2 or < 0.5) in response to spontaneous or oxytocin-stimulated contraction. The most significant changes in phosphorylation were to MYLK on serine 1760, a site associated with reductions in calmodulin binding and subsequent kinase activity. Phosphorylated MYLK (ser1760) increased significantly during spontaneous (9.83 ± 3.27 fold, P < 0.05) and oxytocin -induced (18.56 ± 8.18 fold, P < 0.01) contractions and we were able to validate these data using immunoblotting. Pathway analysis suggested additional proteins involved in calcium signalling, cGMP-PRKG signalling, adrenergic signalling and oxytocin signalling were also phosphorylated during contractions. This study demonstrates that a global phosphoproteomic analysis of myometrial tissue is a sensitive approach to detect changes in the phosphorylation of proteins during myometrial contractions, and provides a platform for further validation of these changes and for identification of their functional significance.

    Research areas

  • Myosin light chain kinase, contractility, uterus, myometrium, phosphoproteomics, parturition

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    Rights statement: This is the author accepted manuscript (AAM). The final published version (version of record) is available online via Elsevier at http://www.sciencedirect.com/science/article/pii/S0006291X16320915. Please refer to any applicable terms of use of the publisher.

    Accepted author manuscript, 531 KB, PDF-document

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