The DICE-binding activity of KH domain 3 of hnRNP K is affected by c-Src-mediated tyrosine phosphorylation.

hnRNP K and hnRNP E1/E2 are RNA-binding proteins comprised of three hnRNP K-homology (KH) domains. These proteins are involved in the translational control and stabilization of mRNAs in erythroid cells. hnRNP E1 and hnRNP K regulate the translation of reticulocyte 15-lipoxygenase (r15-LOX) mRNA. Both proteins bind specifically to the differentiation ...
control element (DICE) in the 3' untranslated region (3'UTR) of the r15-LOX mRNA. It has been shown that hnRNP K is a substrate of the tyrosine kinase c-Src and that tyrosine phosphorylation by c-Src inhibits the binding of hnRNP K to the DICE. Here, we investigate which of the three KH domains of hnRNP E1 and hnRNP K mediate the DICE interaction. Using RNA-binding assays, we demonstrate DICE-binding of the KH domains 1 and 3 of hnRNP E1, and KH domain 3 of hnRNP K. Furthermore, with RNA-binding assays, NMR experiments and in vitro translation studies, we show that tyrosine 458 in KH domain 3 of hnRNP K is important for the DICE interaction and we provide evidence that it is a target of c-Src.
Mesh Terms:
3' Untranslated Regions, Amino Acid Sequence, Arachidonate 15-Lipoxygenase, Heterogeneous-Nuclear Ribonucleoprotein K, Heterogeneous-Nuclear Ribonucleoproteins, Humans, Models, Molecular, Molecular Sequence Data, Nuclear Magnetic Resonance, Biomolecular, Phosphorylation, Protein Binding, Protein Structure, Tertiary, Protein-Tyrosine Kinases, Regulatory Sequences, Nucleic Acid, Transcription, Genetic, Tyrosine, src-Family Kinases
J. Mol. Biol.
Date: Aug. 18, 2006
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