title: SRPK1 inhibition in vivo: modulation of VEGF splicing and potential treatment for multiple diseases.
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.
authors: Microvascular Research Laboratories, Bristol Heart Institute, School of Physiology and Pharmacology, University of Bristol, Bristol, UK. sebastian.oltean@bristol.ac.uk
authors: Sebastian
authors: S
authors: Oltean
authors: Melissa
authors: M
authors: Gammons
authors: Richard
authors: R
authors: Hulse
authors: Maryam
authors: M
authors: Hamdollah-Zadeh
authors: Athina
authors: A
authors: Mavrou
authors: Lucy
authors: L
authors: Donaldson
authors: Andrew H
authors: AH
authors: Salmon
authors: Steve J
authors: SJ
authors: Harper
authors: Michael R
authors: MR
authors: Ladomery
authors: David O
authors: DO
authors: Bates
mesh_terms: D017398:Alternative Splicing / Q000235:genetics; D000818:Animals; D003928:Diabetic Nephropathies / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008268:Macular Degeneration / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
chemical_list: D042461:Vascular Endothelial Growth Factor A; C490215:Srpk1 protein, mouse; D017346:Protein Serine-Threonine Kinases