PMID- 12082117
OWN - NLM
STAT- MEDLINE
DCOM- 20021029
LR  - 20220309
IS  - 0021-9258 (Print)
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Linking)
VI  - 277
IP  - 36
DP  - 2002 Sep 6
TI  - N-terminal tyrosine residues within the potassium channel Kir3 modulate GTPase 
      activity of Galphai.
PG  - 32692-6
AB  - 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.
FAU - Ippolito, Danielle L
AU  - Ippolito DL
AD  - Department of Pharmacology, University of Washington School of Medicine, Seattle, 
      Washington 98195-7280, USA.
FAU - Temkin, Paul A
AU  - Temkin PA
FAU - Rogalski, Sherri L
AU  - Rogalski SL
FAU - Chavkin, Charles
AU  - Chavkin C
LA  - eng
GR  - R37 DA011672/DA/NIDA NIH HHS/United States
GR  - T32 DA007278/DA/NIDA NIH HHS/United States
GR  - T32 GM007270/GM/NIGMS NIH HHS/United States
GR  - GM07270/GM/NIGMS NIH HHS/United States
GR  - DA11672/DA/NIDA NIH HHS/United States
GR  - R01 DA011672/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20020624
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (G Protein-Coupled Inwardly-Rectifying Potassium Channels)
RN  - 0 (Potassium Channels)
RN  - 0 (Potassium Channels, Inwardly Rectifying)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (RGS Proteins)
RN  - 0 (RNA, Complementary)
RN  - 0 (Receptors, Opioid, mu)
RN  - 0RH81L854J (Glutamine)
RN  - 175335-35-0 (RGS4 protein)
RN  - 3WHH0066W5 (Vanadates)
RN  - 42HK56048U (Tyrosine)
RN  - 94ZLA3W45F (Arginine)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatases)
RN  - EC 3.6.1.- (GTP Phosphohydrolases)
RN  - EC 3.6.5.1 (GTP-Binding Protein alpha Subunit, Gi2)
RN  - EC 3.6.5.1 (GTP-Binding Protein alpha Subunits, Gi-Go)
SB  - IM
MH  - Amino Acid Motifs
MH  - Animals
MH  - Arginine/chemistry
MH  - Brain-Derived Neurotrophic Factor/pharmacology
MH  - Catalytic Domain
MH  - Enzyme Activation
MH  - G Protein-Coupled Inwardly-Rectifying Potassium Channels
MH  - GTP Phosphohydrolases/*metabolism
MH  - GTP-Binding Protein alpha Subunit, Gi2
MH  - GTP-Binding Protein alpha Subunits, Gi-Go/metabolism/*physiology
MH  - Glutamine/chemistry
MH  - Hydrolysis
MH  - Kinetics
MH  - Models, Chemical
MH  - Patch-Clamp Techniques
MH  - Potassium Channels/*chemistry/metabolism
MH  - *Potassium Channels, Inwardly Rectifying
MH  - Protein Binding
MH  - Protein Structure, Tertiary
MH  - Protein Tyrosine Phosphatases/metabolism
MH  - Proto-Oncogene Proteins/metabolism/*physiology
MH  - RGS Proteins/metabolism
MH  - RNA, Complementary/metabolism
MH  - Receptor, trkB/metabolism
MH  - Receptors, Opioid, mu/metabolism
MH  - Tyrosine/*chemistry/metabolism
MH  - Vanadates/pharmacology
MH  - Xenopus
PMC - PMC1414899
MID - NIHMS3461
EDAT- 2002/06/26 10:00
MHDA- 2002/10/31 04:00
PMCR- 2008/01/26
CRDT- 2002/06/26 10:00
PHST- 2002/06/26 10:00 [pubmed]
PHST- 2002/10/31 04:00 [medline]
PHST- 2002/06/26 10:00 [entrez]
PHST- 2008/01/26 00:00 [pmc-release]
AID - S0021-9258(20)74410-8 [pii]
AID - 10.1074/jbc.M204407200 [doi]
PST - ppublish
SO  - J Biol Chem. 2002 Sep 6;277(36):32692-6. doi: 10.1074/jbc.M204407200. Epub 2002 
      Jun 24.