SRPK1 inhibition in vivo: Modulation of VEGF splicing and potential treatment for multiple diseases

Sebastian Oltean*, Melissa Gammons, Richard Hulse, Maryam Hamdollah-Zadeh, Athina Mavrou, Lucy Donaldson, Andrew H. Salmon, Steven J Harper, Michael R. Ladomery, David O. Bates

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

27 Citations (Scopus)

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. ©The Authors Journal compilation ©2012 Biochemical Society.

Original languageEnglish
Pages (from-to)831-835
Number of pages5
JournalBiochemical Society Transactions
Volume40
Issue number4
DOIs
Publication statusPublished - 1 Aug 2012

Keywords

  • 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)

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