title: Heterogeneous nuclear ribonucleoprotein K contributes to angiotensin II stimulation of vascular endothelial growth factor mRNA translation.
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 PKCdelta 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.
authors.affiliation: Dept. of Medicine/Nephrology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr., San Antonio, TX, USA. feliers@uthscsa.edu
authors.forename: Denis
authors.initials: D
authors.lastname: Feliers
authors.forename: Myung-Ja
authors.initials: MJ
authors.lastname: Lee
authors.forename: Goutam
authors.initials: G
authors.lastname: Ghosh-Choudhury
authors.forename: Karol
authors.initials: K
authors.lastname: Bomsztyk
authors.forename: B S
authors.initials: BS
authors.lastname: Kasinath
mesh_terms: D020413:3' Untranslated Regions / Q000378:metabolism; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D015152:Blotting, Northern; D002460:Cell Line; D002467:Cell Nucleus / Q000502:physiology*; D016391:Genes, src / Q000235:genetics; D034641:Heterogeneous-Nuclear Ribonucleoprotein K / Q000502:physiology*; D006801:Humans; D047468:Immunoprecipitation; D051379:Mice; D011132:Polyribosomes / Q000378:metabolism; D014176:Protein Biosynthesis / Q000187:drug effects; D051745:Protein Kinase C-delta / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis*; D011994:Recombinant Proteins / Q000494:pharmacology; D013268:Stimulation, Chemical; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; D034641:Heterogeneous-Nuclear Ribonucleoprotein K; D012333:RNA, Messenger; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; D000804:Angiotensin II; D051745:Protein Kinase C-delta