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

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 Commun

journal_title

Nature communications

authors

Burgoyne JR,Rudyk O,Cho HJ,Prysyazhna O,Hathaway N,Weeks A,Evans R,Ng T,Schröder K,Brandes RP,Shah AM,Eaton P

doi

10.1038/ncomms8920

subject

Has Abstract

pub_date

2015-08-10 00:00:00

pages

7920

issn

2041-1723

pii

ncomms8920

journal_volume

6

pub_type

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