SRPK1 inhibition in vivo: modulation of VEGF splicing and potential treatment for multiple diseases. (20th July 2012)

• Record Type: Journal Article
• Authors: Oltean, Sebastian; Gammons, Melissa; Hulse, Richard; Hamdollah-Zadeh, Maryam; Mavrou, Athina; Donaldson, Lucy; Salmon, Andrew H.; Harper, Steve J.; Ladomery, Michael R.; Bates, David O.
• Is Part Of: Biochemical Society transactions. Volume 40:Number 4(2012)
• Page Start: 831
• Page End: 835
• Publication Date: 2012-07-20
• Subjects: age-related macular degeneration -- diabetic nephropathy -- hepatitis C virus -- serine–arginine protein kinase 1 (SRPK1) -- serine/arginine-rich splicing factor 1 (SRSF1) -- vascular endothelial growth factor (VEGF); Biochemistry -- Congresses; 572
• DOI: 10.1042/BST20120051
• Languages: English
• ISSNs: 0300-5127

Abstract

Abstract : 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.