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

doi:10.1038/ncomms8920

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

Guy's and St Thomas' NHS Foundation Trust
King's College London
Goethe University Frankfurt
BHF British Heart Foundation

Research output: Contribution to journal › Article › peer-review

48 Citations (Scopus)

134 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 language	English
Article number	7920
Number of pages	8
Journal	Nature Communications
Volume	6
Issue number	1
Early online date	10 Aug 2015
DOIs	https://doi.org/10.1038/ncomms8920
Publication status	Published - 10 Aug 2015

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This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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10.1038/ncomms8920

Deficient angiogenesis in redox-dead_BURGOYNE Accepted 24Jun2015 GREEN AAM (CC BY)Accepted author manuscript, 12.9 MBLicence: CC BY

Cite this

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title = "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.",

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AU - Burgoyne, Joe

AU - Rudyk, Olena

AU - Cho, Hyun Ju

AU - Prysyazhna, Oleksandra

AU - Hathaway, Natasha

AU - Weeks, Amanda

AU - Evans, Rachel

AU - Ng, Tony

AU - Schröder, Katrin

AU - Brandes, Ralf P.

AU - Shah, Ajay M.

AU - Eaton, Philip

PY - 2015/8/10

Y1 - 2015/8/10

N2 - 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.

AB - 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.

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DO - 10.1038/ncomms8920

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IS - 1

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ER -

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

Abstract

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