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Deficient angiogenesis in redox-dead Cys17Ser PKARIα knock-in mice

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Listed:
  • Joseph R. Burgoyne

    (King’s College London, The British Heart Foundation Centre of Excellence, The Rayne Institute, Saint Thomas’ Hospital)

  • Olena Rudyk

    (King’s College London, The British Heart Foundation Centre of Excellence, The Rayne Institute, Saint Thomas’ Hospital)

  • Hyun-ju Cho

    (King’s College London, The British Heart Foundation Centre of Excellence, The Rayne Institute, Saint Thomas’ Hospital)

  • Oleksandra Prysyazhna

    (King’s College London, The British Heart Foundation Centre of Excellence, The Rayne Institute, Saint Thomas’ Hospital)

  • Natasha Hathaway

    (King’s College London, The British Heart Foundation Centre of Excellence, The Rayne Institute, Saint Thomas’ Hospital)

  • Amanda Weeks

    (King’s College London, The Rayne Institute, Saint Thomas’ Hospital)

  • Rachel Evans

    (King’s College London, 2nd Floor, New Hunt's House, Guy’s Medical School Campus)

  • Tony Ng

    (King’s College London, 2nd Floor, New Hunt's House, Guy’s Medical School Campus)

  • Katrin Schröder

    (Institut für Kardiovaskuläre Physiologie, Goethe-Universität)

  • Ralf P. Brandes

    (Institut für Kardiovaskuläre Physiologie, Goethe-Universität)

  • Ajay M. Shah

    (King’s College London, The British Heart Foundation Centre of Excellence, The James Black Centre, Denmark Hill Campus)

  • Philip Eaton

    (King’s College London, The British Heart Foundation Centre of Excellence, The Rayne Institute, Saint Thomas’ Hospital)

Abstract

Angiogenesis is essential for tissue development, wound healing and tissue perfusion, with its dysregulation linked to tumorigenesis, rheumatoid arthritis and heart disease. Here we show that pro-angiogenic stimuli couple to NADPH oxidase-dependent generation of oxidants that catalyse an activating intermolecular-disulphide between regulatory-RIα subunits of protein kinase A (PKA), which stimulates PKA-dependent ERK signalling. This is crucial to blood vessel growth as ‘redox-dead’ Cys17Ser RIα knock-in mice fully resistant to PKA disulphide-activation have deficient angiogenesis in models of hind limb ischaemia and tumour-implant growth. Disulphide-activation of PKA represents a new therapeutic target in diseases with aberrant angiogenesis.

Suggested Citation

  • Joseph R. Burgoyne & Olena Rudyk & Hyun-ju Cho & Oleksandra Prysyazhna & Natasha Hathaway & Amanda Weeks & Rachel Evans & Tony Ng & Katrin Schröder & Ralf P. Brandes & Ajay M. Shah & Philip Eaton, 2015. "Deficient angiogenesis in redox-dead Cys17Ser PKARIα knock-in mice," Nature Communications, Nature, vol. 6(1), pages 1-8, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8920
    DOI: 10.1038/ncomms8920
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