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Accession IconGSE70216

Differential gene expression to VEGF in aorta from wild-type and C17S PKARI knock-in mice

Organism Icon Mus musculus
Sample Icon 12 Downloadable Samples
Technology Badge Icon Affymetrix Mouse Gene 2.0 ST Array (mogene20st)

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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 pro-angiogenic stimuli couple to NADPH oxidase-dependent generation of oxidants that catalyse an activating intermolecular-disulphide between regulatory-RI subunits of protein kinase A (PKA), which stimulates PKA-dependent ERK signalling. This is crucial to blood vessel growth as 'redox-dead' Cys17Ser RI 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.
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