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.
N-terminal tyrosine residues within the potassium channel Kir3 modulate GTPase activity of Galphai.
Ippolito DL, Temkin PA, Rogalski SL, Chavkin C.
???displayArticle.abstract??? trkB activation results in tyrosine phosphorylation of N-terminal Kir3 residues, decreasing channel activation. To determine the mechanism of this effect, we reconstituted Kir3, trkB, and the mu opioid receptor in Xenopus oocytes. Activation of trkB by BDNF (brain-derived neurotrophic factor) accelerated Kir3 deactivation following termination of mu opioid receptor signaling. Similarly, overexpression of RGS4, a GTPase-activating protein (GAP), accelerated Kir3 deactivation. Blocking GTPase activity with GTPgammaS also prevented Kir3 deactivation, and the GTPgammaS effect was not reversed by BDNF treatment. These results suggest that BDNF treatment did not reduce Kir3 affinity for Gbetagamma but rather acted to accelerate GTPase activity, like RGS4. Tyrosine phosphatase inhibition by peroxyvanadate pretreatment reversibly mimicked the BDNF/trkB effect, indicating that tyrosine phosphorylation of Kir3 may have caused the GTPase acceleration. Tyrosine to phenylalanine substitution in the N-terminal domain of Kir3.4 blocked the BDNF effect, supporting the hypothesis that phosphorylation of these tyrosines was responsible. Like other GAPs, Kir3.4 contains a tyrosine-arginine-glutamine motif that is thought to function by interacting with G protein catalytic domains to facilitate GTP hydrolysis. These data suggest that the N-terminal tyrosine hydroxyls in Kir3 normally mask the GAP activity and that modification by phosphorylation or phenylalanine substitution reveals the GAP domain. Thus, BDNF activation of trkB could inhibit Kir3 by facilitating channel deactivation.
Alleva,
Psychosocial vs. "physical" stress situations in rodents and humans: role of neurotrophins.
2001, Pubmed
Alleva,
Psychosocial vs. "physical" stress situations in rodents and humans: role of neurotrophins.
2001,
Pubmed Bowlby,
Modulation of the Kv1.3 potassium channel by receptor tyrosine kinases.
1997,
Pubmed Cabot,
Immune cell-derived beta-endorphin. Production, release, and control of inflammatory pain in rats.
1997,
Pubmed Cabot,
Methionine-enkephalin-and Dynorphin A-release from immune cells and control of inflammatory pain.
2001,
Pubmed Dascal,
Involvement of a GTP-binding protein in mediation of serotonin and acetylcholine responses in Xenopus oocytes injected with rat brain messenger RNA.
1986,
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 Felsch,
Activation of protein tyrosine kinase PYK2 by the m1 muscarinic acetylcholine receptor.
1998,
Pubmed Haendeler,
Angiotensin II mediated signal transduction. Important role of tyrosine kinases.
2000,
Pubmed He,
Identification of a potassium channel site that interacts with G protein betagamma subunits to mediate agonist-induced signaling.
1999,
Pubmed Holmes,
Tyrosine phosphorylation of the Kv1.3 potassium channel.
1996,
Pubmed Holmes,
Association of Src tyrosine kinase with a human potassium channel mediated by SH3 domain.
1996,
Pubmed Huang,
Tyrosine kinase-dependent suppression of a potassium channel by the G protein-coupled m1 muscarinic acetylcholine receptor.
1993,
Pubmed
,
Xenbase Huang,
Binding of the G protein betagamma subunit to multiple regions of G protein-gated inward-rectifying K+ channels.
1997,
Pubmed Huang,
Evidence that direct binding of G beta gamma to the GIRK1 G protein-gated inwardly rectifying K+ channel is important for channel activation.
1995,
Pubmed
,
Xenbase Huang,
Direct activation of inward rectifier potassium channels by PIP2 and its stabilization by Gbetagamma.
1998,
Pubmed
,
Xenbase Ikeda,
Involvement of G-protein-activated inwardly rectifying K (GIRK) channels in opioid-induced analgesia.
2000,
Pubmed Ishii,
PIP3 inhibition of RGS protein and its reversal by Ca2+/calmodulin mediate voltage-dependent control of the G protein cycle in a cardiac K+ channel.
2002,
Pubmed Keren-Raifman,
Expression levels of RGS7 and RGS4 proteins determine the mode of regulation of the G protein-activated K(+) channel and control regulation of RGS7 by G beta 5.
2001,
Pubmed
,
Xenbase Kobrinsky,
Receptor-mediated hydrolysis of plasma membrane messenger PIP2 leads to K+-current desensitization.
2000,
Pubmed
,
Xenbase Kovoor,
Co-expression of Gbeta5 enhances the function of two Ggamma subunit-like domain-containing regulators of G protein signaling proteins.
2000,
Pubmed
,
Xenbase Kovoor,
Gi Irks GIRKs.
2002,
Pubmed Lesage,
Molecular properties of neuronal G-protein-activated inwardly rectifying K+ channels.
1995,
Pubmed
,
Xenbase Ling,
Enhanced activity of a large conductance, calcium-sensitive K+ channel in the presence of Src tyrosine kinase.
2000,
Pubmed Mannion,
Neurotrophins: peripherally and centrally acting modulators of tactile stimulus-induced inflammatory pain hypersensitivity.
1999,
Pubmed Mosser,
Kinetic analysis of M2 muscarinic receptor activation of Gi in Sf9 insect cell membranes.
2002,
Pubmed Nassar,
Structures of Cdc42 bound to the active and catalytically compromised forms of Cdc42GAP.
1998,
Pubmed Nissen,
Crystal structure of the ternary complex of Phe-tRNAPhe, EF-Tu, and a GTP analog.
1995,
Pubmed Peleg,
G(alpha)(i) controls the gating of the G protein-activated K(+) channel, GIRK.
2002,
Pubmed
,
Xenbase Rak,
Crystal structure of the GAP domain of Gyp1p: first insights into interaction with Ypt/Rab proteins.
2000,
Pubmed Rittinger,
Structure at 1.65 A of RhoA and its GTPase-activating protein in complex with a transition-state analogue.
1997,
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 Scheffzek,
The Ras-RasGAP complex: structural basis for GTPase activation and its loss in oncogenic Ras mutants.
1997,
Pubmed Seewald,
RanGAP mediates GTP hydrolysis without an arginine finger.
2002,
Pubmed Sprang,
G proteins, effectors and GAPs: structure and mechanism.
1997,
Pubmed Sprang,
GAP into the breach.
1997,
Pubmed Srinivasa,
Mechanism of RGS4, a GTPase-activating protein for G protein alpha subunits.
1998,
Pubmed Sui,
Activation of the atrial KACh channel by the betagamma subunits of G proteins or intracellular Na+ ions depends on the presence of phosphatidylinositol phosphates.
1998,
Pubmed
,
Xenbase Tesmer,
Structure of RGS4 bound to AlF4--activated G(i alpha1): stabilization of the transition state for GTP hydrolysis.
1997,
Pubmed Vetter,
The guanine nucleotide-binding switch in three dimensions.
2001,
Pubmed Vivaudou,
Probing the G-protein regulation of GIRK1 and GIRK4, the two subunits of the KACh channel, using functional homomeric mutants.
1997,
Pubmed
,
Xenbase Woolf,
Transcriptional and posttranslational plasticity and the generation of inflammatory pain.
1999,
Pubmed Yi,
Controlling potassium channel activities: Interplay between the membrane and intracellular factors.
2001,
Pubmed Yu,
NMDA channel regulation by channel-associated protein tyrosine kinase Src.
1997,
Pubmed
