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

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

Biochem Soc Trans. 2012 Aug 1;40(4):831-5

Authors: Oltean S, Gammons M, Hulse R, Hamdollah-Zadeh M, Mavrou A, Donaldson L, Salmon AH, Harper SJ, Ladomery MR, Bates DO

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.

PMID: 22817743 [PubMed - in process]

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