Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
J Biol Chem
2005 Dec 16;28050:41683-93. doi: 10.1074/jbc.M507069200.
Show Gene links
Show Anatomy links
Tyrosine phosphorylation of K(ir)3.1 in spinal cord is induced by acute inflammation, chronic neuropathic pain, and behavioral stress.
Ippolito DL
,
Xu M
,
Bruchas MR
,
Wickman K
,
Chavkin C
.
???displayArticle.abstract???
Tyrosine phosphorylation is an important means of regulating ion channel function. Our previous gene expression studies using the Xenopus laevis oocyte system suggested that tyrosine phosphorylation of G-protein-gated inwardly rectifying potassium channels (K(ir)3 or GIRK) suppressed basal channel conductance and accelerated channel deactivation. To assess whether similar mechanisms regulate K(ir)3 function in mammalian cells, we developed and characterized a phosphoselective antibody recognizing K(ir)3.1 phosphorylated at tyrosine 12 in the N-terminal domain and then probed for evidence of K(ir)3.1 phosphorylation in cultured mammalian cells and spinal cord. The antibody was found to discriminate between the phospho-Tyr(12) of K(ir)3.1 and the native state in transfected cell lines and in primary cultures of mouse atria. Following either mouse hindpaw formalin injection or sciatic nerve ligation, pY12-K(ir)3.1 immunoreactivity was enhanced unilaterally in the superficial layers of the spinal cord dorsal horn, regions previously described as expressing K(ir)3.1 channels. Mice lacking K 3.1 following targeted gene disruption did not show specific pY12-K(ir)3.1 immunoreactivity after sciatic nerve ligation. Further, mice exposed to repeatedly forced swim stress showed bilateral enhancement in pY12-K(ir)3.1 in the dorsal horn. This study provides evidence that K(ir)3 tyrosine phosphorylation occurred during acute and chronic inflammatory pain and under behavioral stress. The reduction in K(ir)3 channel activity is predicted to enhance neuronal excitability under physiologically relevant conditions and may mediate a component of the adaptive physiological response.
Ahmadian,
Tyrosine phosphorylation of GluR2 is required for insulin-stimulated AMPA receptor endocytosis and LTD.
2004, Pubmed
Ahmadian,
Tyrosine phosphorylation of GluR2 is required for insulin-stimulated AMPA receptor endocytosis and LTD.
2004,
Pubmed
Belcheva,
mu-Opioid receptor-mediated ERK activation involves calmodulin-dependent epidermal growth factor receptor transactivation.
2001,
Pubmed
Berrino,
Antinociceptive effect in mice of intraperitoneal N-methyl-D-aspartate receptor antagonists in the formalin test.
2003,
Pubmed
Bettahi,
Contribution of the Kir3.1 subunit to the muscarinic-gated atrial potassium channel IKACh.
2002,
Pubmed
Blom,
Sequence and structure-based prediction of eukaryotic protein phosphorylation sites.
1999,
Pubmed
Celver,
Distinct domains of the mu-opioid receptor control uncoupling and internalization.
2004,
Pubmed
,
Xenbase
Chan,
Control of channel activity through a unique amino acid residue of a G protein-gated inwardly rectifying K+ channel subunit.
1996,
Pubmed
,
Xenbase
Dascal,
Signalling via the G protein-activated K+ channels.
1997,
Pubmed
Doupnik,
RGS proteins reconstitute the rapid gating kinetics of gbetagamma-activated inwardly rectifying K+ channels.
1997,
Pubmed
,
Xenbase
Elvan,
Right ventricular infarction causes heterogeneous autonomic denervation of the viable peri-infarct area.
1998,
Pubmed
Garraway,
BDNF sensitizes the response of lamina II neurons to high threshold primary afferent inputs.
2003,
Pubmed
Hsu,
p38 mitogen-activated protein kinase is involved in Fas ligand expression.
1999,
Pubmed
Huang,
Trk receptors: roles in neuronal signal transduction.
2003,
Pubmed
Ippolito,
N-terminal tyrosine residues within the potassium channel Kir3 modulate GTPase activity of Galphai.
2002,
Pubmed
,
Xenbase
Ji,
Cell signaling and the genesis of neuropathic pain.
2004,
Pubmed
Kofuji,
Potassium buffering in the central nervous system.
2004,
Pubmed
Li,
Alterations in spinal cord gene expression after hindpaw formalin injection.
2004,
Pubmed
Liu,
Stress induces activation of stress-activated kinases in the mouse brain.
2004,
Pubmed
Ma,
Diverse trafficking patterns due to multiple traffic motifs in G protein-activated inwardly rectifying potassium channels from brain and heart.
2002,
Pubmed
Marker,
Spinal G-protein-gated K+ channels formed by GIRK1 and GIRK2 subunits modulate thermal nociception and contribute to morphine analgesia.
2004,
Pubmed
Marker,
Spinal G-protein-gated potassium channels contribute in a dose-dependent manner to the analgesic effect of mu- and delta- but not kappa-opioids.
2005,
Pubmed
McLaughlin,
Phosphorylation of a carboxyl-terminal serine within the kappa-opioid receptor produces desensitization and internalization.
2003,
Pubmed
,
Xenbase
Nishida,
Structural basis of inward rectification: cytoplasmic pore of the G protein-gated inward rectifier GIRK1 at 1.8 A resolution.
2002,
Pubmed
Paz,
Attenuation of anaphylactic shock and related mortality in guinea-pigs after administration of a potent protein kinase inhibitor, K252a.
1991,
Pubmed
Peleg,
G(alpha)(i) controls the gating of the G protein-activated K(+) channel, GIRK.
2002,
Pubmed
,
Xenbase
Porsolt,
Depression: a new animal model sensitive to antidepressant treatments.
1977,
Pubmed
Rhee,
Hydrogen peroxide: a key messenger that modulates protein phosphorylation through cysteine oxidation.
2000,
Pubmed
Rhee,
Redox signaling: hydrogen peroxide as intracellular messenger.
1999,
Pubmed
Rogalski,
TrkB activation by brain-derived neurotrophic factor inhibits the G protein-gated inward rectifier Kir3 by tyrosine phosphorylation of the channel.
2000,
Pubmed
,
Xenbase
Roux,
ERK and p38 MAPK-activated protein kinases: a family of protein kinases with diverse biological functions.
2004,
Pubmed
Salter,
Src kinases: a hub for NMDA receptor regulation.
2004,
Pubmed
Seltzer,
A novel behavioral model of neuropathic pain disorders produced in rats by partial sciatic nerve injury.
1990,
Pubmed
Takano,
Role of protein-tyrosine kinase syk in oxidative stress signaling in B cells.
2002,
Pubmed
Taylor,
Opioid inhibition of formalin-induced changes in plasma extravasation and local blood flow in rats.
2000,
Pubmed
Tong,
Tyrosine decaging leads to substantial membrane trafficking during modulation of an inward rectifier potassium channel.
2001,
Pubmed
,
Xenbase
Torrecilla,
G-protein-gated potassium channels containing Kir3.2 and Kir3.3 subunits mediate the acute inhibitory effects of opioids on locus ceruleus neurons.
2002,
Pubmed
Tucker,
Neurotrophin modulation of voltage-gated potassium channels in rat through TrkB receptors is time and sensory experience dependent.
2002,
Pubmed
Wang,
gadd45 is not required for activation of c-Jun N-terminal kinase or p38 during acute stress.
1999,
Pubmed
Wickman,
Abnormal heart rate regulation in GIRK4 knockout mice.
1998,
Pubmed
Woolf,
Neuronal plasticity: increasing the gain in pain.
2000,
Pubmed
Woolf,
Transcriptional and posttranslational plasticity and the generation of inflammatory pain.
1999,
Pubmed
Xu,
Neuropathic pain activates the endogenous kappa opioid system in mouse spinal cord and induces opioid receptor tolerance.
2004,
Pubmed
Zimmermann,
Ethical guidelines for investigations of experimental pain in conscious animals.
1983,
Pubmed