Heterogeneous nuclear ribonucleoprotein K contributes to angiotensin II stimulation of vascular endothelial growth factor mRNA translation.
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.
Feliers
Denis
D
Dept. of Medicine/Nephrology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr., San Antonio, TX, USA. feliers@uthscsa.edu
Lee
Myung-Ja
MJ
Ghosh-Choudhury
Goutam
G
Bomsztyk
Karol
K
Kasinath
B S
BS
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*
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