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.
journal_name
Nat Communjournal_title
Nature communicationsauthors
Burgoyne JR,Rudyk O,Cho HJ,Prysyazhna O,Hathaway N,Weeks A,Evans R,Ng T,Schröder K,Brandes RP,Shah AM,Eaton Pdoi
10.1038/ncomms8920subject
Has Abstractpub_date
2015-08-10 00:00:00pages
7920issn
2041-1723pii
ncomms8920journal_volume
6pub_type
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