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

Joe 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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

37 Citations (Scopus)
107 Downloads (Pure)

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.

Original languageEnglish
Article number7920
Number of pages8
JournalNature Communications
Volume6
Issue number1
Early online date10 Aug 2015
DOIs
Publication statusPublished - 10 Aug 2015

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