Heterogeneous nuclear ribonucleoprotein K contributes to angiotensin II stimulation of vascular endothelial growth factor mRNA translation

Denis Feliers, Myung Ja Lee, Goutam Ghosh-Choudhury, Karol Bomsztyk, B. S. Kasinath

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

ANG II rapidly increases VEGF synthesis in proximal tubular epithelial cells through mRNA translation. The role of heterogeneous nuclear ribonucleoprotein K (hnRNP K) in ANG II regulation of VEGF mRNA translation initiation was examined. ANG II activated hnRNP K as judged by binding to poly(C)- and poly(U)-agarose. ANG II increased hnRNP K binding to VEGF mRNA at the same time as it stimulated its translation, suggesting that hnRNP K contributes to VEGF mRNA translation. Inhibition of hnRNP K expression by RNA interference significantly reduced ANG II stimulation of VEGF synthesis. ANG II increased hnRNP K phosphorylation on both tyrosine and serine residues with distinct time courses; only Ser302 phosphorylation paralleled binding to VEGF mRNA. Src inhibition using PP2 or RNA interference inhibited PKCδ activity and prevented hnRNP K phosphorylation on both tyrosine and serine residues and its binding to VEGF mRNA. Under these conditions, ANG II-induced VEGF synthesis was inhibited. ANG II treatment induced redistribution of both VEGF mRNA and hnRNP K protein from light to heavy polysomal fractions, suggesting increased binding of hnRNP K to VEGF mRNA that is targeted for increased translation. This study shows that hnRNP K augments efficiency of VEGF mRNA translation stimulated by ANG II.

Original languageEnglish (US)
Pages (from-to)F607-F615
JournalAmerican Journal of Physiology - Renal Physiology
Volume293
Issue number2
DOIs
StatePublished - Aug 1 2007

Keywords

  • ANG II
  • RNA-binding protein
  • Signal transduction
  • VEGF

ASJC Scopus subject areas

  • Physiology
  • Urology

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