+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

G protein-coupled receptor kinase 2-mediated phosphorylation of downstream regulatory element antagonist modulator regulates membrane trafficking of Kv4.2 potassium channel



G protein-coupled receptor kinase 2-mediated phosphorylation of downstream regulatory element antagonist modulator regulates membrane trafficking of Kv4.2 potassium channel



Journal of Biological Chemistry 282(2): 1205-1215



Downstream regulatory element antagonist modulator (DREAM)/potassium channel interacting protein (KChIP3) is a multifunctional protein of the neuronal calcium sensor subfamily of Ca2+-binding proteins with specific roles in different cell compartments. In the nucleus, DREAM acts as a Ca2+-dependent transcriptional repressor, and outside the nucleus DREAM interacts with Kv4 potassium channels, regulating their trafficking to the cell membrane and their gating properties. In this study we characterized the interaction of DREAM with GRK6 and GRK2, members of the G protein-coupled receptor kinase family of proteins, and their phosphorylation of DREAM. Ser-95 was identified as the site phosphorylated by GRK2. This phosphorylation did not modify the repressor activity of DREAM. Mutation of Ser-95 to aspartic acid, however, blocked DREAM-mediated membrane expression of the Kv4.2 potassium channel without affecting channel tetramerization. Treatment with the calcineurin inhibitors FK506 and cyclosporin A also blocked DREAM-mediated Kv4.2 channel trafficking and calcineurin de-phosphorylated GRK2-phosphorylated DREAM in vitro. Our results indicate that these two Ca2+-dependent posttranslational events regulate the activity of DREAM on Kv4.2 channel function.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 012975336

Download citation: RISBibTeXText

PMID: 17102134

DOI: 10.1074/jbc.m607166200


Related references

The regulation of apoptosis by the downstream regulatory element antagonist modulator/potassium channel interacting protein 3 (DREAM/KChIP3) through interactions with hexokinase I. Biochemical and Biophysical Research Communications 433(4): 508-512, 2013

Day-night changes in downstream regulatory element antagonist modulator/potassium channel interacting protein activity contribute to circadian gene expression in pineal gland. Journal of Neuroscience 24(23): 5346-5355, 2004

G protein-coupled receptor kinase-mediated phosphorylation regulates post-endocytic trafficking of the D2 dopamine receptor. Journal of Biological Chemistry 284(22): 15038-15051, 2009

Downstream regulatory element antagonist modulator regulates Ca2+ homeostasis and viability in cerebellar neurons. Journal of Neuroscience 25(47): 10822-10830, 2005

Regulatory actions of the A-kinase anchoring protein Yotiao on a heart potassium channel downstream of PKA phosphorylation. Proceedings of the National Academy of Sciences of the United States of America 101(46): 16374-8, 2004

Phosphorylation of the voltage-gated potassium channel Kv2.1 by AMP-activated protein kinase regulates membrane excitability. Proceedings of the National Academy of Sciences of the United States of America 108(44): 18132-7, 2011

G protein-coupled receptor-mediated phosphorylation of the activation loop of protein kinase D: dependence on plasma membrane translocation and protein kinase Cepsilon. Journal of Biological Chemistry 279(33): 34361-34372, 2004

Ca2+-activated nucleotidase 1, a novel target gene for the transcriptional repressor DREAM (downstream regulatory element antagonist modulator), is involved in protein folding and degradation. Journal of Biological Chemistry 287(22): 18478-18491, 2012

Protein kinase A-mediated phosphorylation of serine 357 of the mouse prostacyclin receptor regulates its coupling to G s -, to G i -, and to G q -coupled effector signaling. Journal of Biological Chemistry 293(28): 11046, 2018

Protein kinase A-mediated phosphorylation of serine 357 of the mouse prostacyclin receptor regulates its coupling to G(s)-, to G(i)-, and to G(q)-coupled effector signaling. Journal of Biological Chemistry 276(36): 33596-33607, 2001

Involvement of G protein-coupled receptor kinase and protein kinase C phosphorylation sites in alpha-1B adrenergic receptor trafficking and function. FASEB Journal 15(4): A576, 2001

Ca2+ and Mg2+ modulate conformational dynamics and stability of downstream regulatory element antagonist modulator. Protein Science 24(5): 741-751, 2015

Downstream regulatory element antagonistic modulator regulates islet prodynorphin expression. American Journal of Physiology. Endocrinology and Metabolism 291(3): E587-E595, 2006

Downstream Regulatory Element Antagonist Modulator (DREAM), a target for anti-thrombotic agents. Pharmacological Research 117: 283-287, 2017

DREAM (downstream regulatory element antagonist modulator) contributes to synaptic depression and contextual fear memory. Molecular Brain 3: 3, 2010