Protein kinase A enhances, whereas glycogen synthase kinase-3 beta inhibits, the activity of the exon 2-encoded transactivator domain of heterogeneous nuclear ribonucleoprotein D in a hierarchical fashion

The Biochemical Journal
Mate TolnayGeorge C Tsokos

Abstract

Heterogeneous nuclear ribonucleoprotein D (hnRNP D) is implicated in transcriptional regulation. Alternative splicing of exons 2 and 7 generates four isoforms of the protein. We report here that only isoforms that contain the product of exon 2 (amino acids 79-97) were able to transactivate. Moreover, the exon 2-encoded protein domain alone was sufficient to drive transcription. TATA-binding protein and p300 interacted with a synthetic peptide corresponding to exon 2, and both proteins co-precipitated with hnRNP D. Stimulation of protein kinase A (PKA) and protein kinase C (PKC) synergistically induced the transactivating ability of hnRNP D, and the exon 2-encoded domain was sufficient for this inducibility. In kinase assays PKA phosphorylated Ser-87 of hnRNP D, whereas glycogen synthase kinase-3 beta (GSK-3 beta) phosphorylated Ser-83, but only if Ser-87 had been pre-phosphorylated by PKA. Phosphorylation of Ser-87 enhanced, whereas phosphorylation of Ser-83 repressed, transactivation. Overexpression of GSK-3 beta inhibited transactivation by hnRNP D, but stimulation of PKC negated the inhibitory effect of GSK-3 beta. We suggest that a hierarchical phosphorylation pathway regulates the transactivating ability of hnRNP D: PKA ac...Continue Reading

References

Dec 16, 1992·Biochimica Et Biophysica Acta·S E PlyteJ R Woodgett
Jan 1, 1993·Annual Review of Biochemistry·G DreyfussC G Burd
May 24, 1996·The Journal of Biological Chemistry·C T DeMaria, G Brewer
Sep 17, 1996·Proceedings of the National Academy of Sciences of the United States of America·H Eldar-FinkelmanE G Krebs
Dec 10, 1998·Nucleic Acids Research·A KreegipuuS Brunak
Jul 8, 1999·Current Opinion in Cell Biology·A M Krecic, M S Swanson
Nov 5, 1999·Journal of Molecular Biology·P E Wright, H J Dyson
Nov 24, 1999·The Journal of Biological Chemistry·G M WilsonG Brewer
Oct 6, 2000·The Journal of Biological Chemistry·L W Yuan, J E Gambee
Nov 7, 2000·The Journal of Biological Chemistry·J W Neal, N A Clipstone

❮ Previous
Next ❯

Citations

Jun 2, 2011·International Journal of Alzheimer's Disease·Calum Sutherland
Jul 23, 2003·The Journal of Biological Chemistry·Francesca DemarchiClaudio Schneider
Jun 24, 2003·The Journal of Biological Chemistry·Gerald M WilsonGary Brewer
Aug 21, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yuang-Taung JuangGeorge C Tsokos
Nov 22, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Mate TolnayGeorge C Tsokos
Oct 21, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Klaus TenbrockGeorge C Tsokos
Dec 28, 2005·Biochimica Et Biophysica Acta·Brian CarpenterGraeme I Murray
Apr 24, 2010·Brain, Behavior, and Immunity·Melissa D LaJevicDonald A Chambers

❮ Previous
Next ❯

Related Concepts

Related Feeds

Alternative splicing

Alternative splicing a regulated gene expression process that allows a single genetic sequence to code for multiple proteins. Here is that latest research.