SRPK1 (serine–arginine protein kinase 1) is a protein kinase that specifically phosphorylates proteins containing serine–arginine-rich domains. Its substrates include a family of SR proteins that are key regulators of mRNA AS (alternative splicing). VEGF (vascular endothelial growth factor), a principal angiogenesis factor contains an alternative 3′ splice site in the terminal exon that defines a family of isoforms with a different amino acid sequence at the C-terminal end, resulting in anti-angiogenic activity in the context of VEGF165-driven neovascularization. It has been shown recently in our laboratories that SRPK1 regulates the choice of this splice site through phosphorylation of the splicing factor SRSF1 (serine/arginine-rich splicing factor 1). The present review summarizes progress that has been made to understand how SRPK1 inhibition may be used to manipulate the balance of pro- and anti-angiogenic VEGF isoforms in animal models in vivo and therefore control abnormal angiogenesis and other pathophysiological processes in multiple disease states.
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August 2012
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Conference Article|
July 20 2012
SRPK1 inhibition in vivo: modulation of VEGF splicing and potential treatment for multiple diseases
Sebastian Oltean;
Sebastian Oltean
1
*Microvascular Research Laboratories, Bristol Heart Institute, School of Physiology and Pharmacology, University of Bristol, Southwell Street, Bristol BS2 8EJ, U.K.
1To whom correspondence should be addressed (emailsebastian.oltean@bristol.ac.uk).
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Melissa Gammons;
Melissa Gammons
*Microvascular Research Laboratories, Bristol Heart Institute, School of Physiology and Pharmacology, University of Bristol, Southwell Street, Bristol BS2 8EJ, U.K.
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Richard Hulse;
Richard Hulse
*Microvascular Research Laboratories, Bristol Heart Institute, School of Physiology and Pharmacology, University of Bristol, Southwell Street, Bristol BS2 8EJ, U.K.
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Maryam Hamdollah-Zadeh;
Maryam Hamdollah-Zadeh
*Microvascular Research Laboratories, Bristol Heart Institute, School of Physiology and Pharmacology, University of Bristol, Southwell Street, Bristol BS2 8EJ, U.K.
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Athina Mavrou;
Athina Mavrou
*Microvascular Research Laboratories, Bristol Heart Institute, School of Physiology and Pharmacology, University of Bristol, Southwell Street, Bristol BS2 8EJ, U.K.
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Lucy Donaldson;
Lucy Donaldson
†School of Physiology and Pharmacology, University of Bristol, Southwell Street, Bristol BS2 8EJ, U.K.
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Andrew H. Salmon;
Andrew H. Salmon
*Microvascular Research Laboratories, Bristol Heart Institute, School of Physiology and Pharmacology, University of Bristol, Southwell Street, Bristol BS2 8EJ, U.K.
‡Academic Renal Unit, Clinical Science at North Bristol, University of Bristol, Bristol BS10 5NB, U.K.
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Steve J. Harper;
Steve J. Harper
*Microvascular Research Laboratories, Bristol Heart Institute, School of Physiology and Pharmacology, University of Bristol, Southwell Street, Bristol BS2 8EJ, U.K.
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Michael R. Ladomery;
Michael R. Ladomery
§Centre for Research in Biomedicine, Faculty of Health and Life Sciences, University of the West of England, Coldharbour Lane, Bristol BS16 1QY, U.K.
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David O. Bates
David O. Bates
*Microvascular Research Laboratories, Bristol Heart Institute, School of Physiology and Pharmacology, University of Bristol, Southwell Street, Bristol BS2 8EJ, U.K.
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Biochem Soc Trans (2012) 40 (4): 831–835.
Article history
Received:
March 01 2012
Citation
Sebastian Oltean, Melissa Gammons, Richard Hulse, Maryam Hamdollah-Zadeh, Athina Mavrou, Lucy Donaldson, Andrew H. Salmon, Steve J. Harper, Michael R. Ladomery, David O. Bates; SRPK1 inhibition in vivo: modulation of VEGF splicing and potential treatment for multiple diseases. Biochem Soc Trans 1 August 2012; 40 (4): 831–835. doi: https://doi.org/10.1042/BST20120051
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