| First Author | Burgoyne JR | Year | 2015 |
| Journal | Nat Commun | Volume | 6 |
| Pages | 7920 | PubMed ID | 26258640 |
| Mgi Jnum | J:224999 | Mgi Id | MGI:5689951 |
| Doi | 10.1038/ncomms8920 | Citation | Burgoyne JR, et al. (2015) Deficient angiogenesis in redox-dead Cys17Ser PKARIalpha knock-in mice. Nat Commun 6:7920 |
| abstractText | 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-RIalpha subunits of protein kinase A (PKA), which stimulates PKA-dependent ERK signalling. This is crucial to blood vessel growth as 'redox-dead' Cys17Ser RIalpha 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. |
