PMID- 10318802
OWN - NLM
STAT- MEDLINE
DCOM- 19990617
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 20
DP  - 1999 May 14
TI  - Protein kinase A phosphorylation alters Kvbeta1.3 subunit-mediated inactivation
      of the Kv1.5 potassium channel.
PG  - 13928-32
AB  - The human Kv1.5 potassium channel forms the IKur current in atrial myocytes and
      is functionally altered by coexpression with Kvbeta subunits. To explore the role
      of protein kinase A (PKA) phosphorylation in beta-subunit function, we examined
      the effect of PKA stimulation on Kv1.5 current following coexpression with either
      Kvbeta1.2 or Kvbeta1.3, both of which coassemble with Kv1.5 and induce fast
      inactivation. In Xenopus oocytes expressing Kv1.5 and Kvbeta1.3, activation of
      PKA reduced macroscopic inactivation with an increase in K+ current. Similar
      results were obtained using HEK 293 cells which lack endogenous K+ channel
      subunits. These effects did not occur when Kv1.5 was coexpressed with either
      Kvbeta1.2 or Kvbeta1.3 lacking the amino terminus, suggesting involvement of this
      region of Kvbeta1.3. Removal of a consensus PKA phosphorylation site on the
      Kvbeta1.3 NH2 terminus (serine 24), but not alternative sites in either Kvbeta1.3
      or Kv1.5, resulted in loss of the functional effects of kinase activation. The
      effects of phosphorylation appeared to be electrostatic, as replacement of serine
      24 with a negatively charged amino acid reduced beta-mediated inactivation, while
      substitution with a positively charged residue enhanced it. These results
      indicate that Kvbeta1.3-induced inactivation is reduced by PKA activation, and
      that phosphorylation of serine 24 in the subunit NH2 terminus is responsible.
FAU - Kwak, Y G
AU  - Kwak YG
AD  - Department of Physiology and Biochemistry and Molecular Biology, Colorado State
      University, Ft. Collins, Colorado 80523, USA.
FAU - Hu, N
AU  - Hu N
FAU - Wei, J
AU  - Wei J
FAU - George, A L Jr
AU  - George AL Jr
FAU - Grobaski, T D
AU  - Grobaski TD
FAU - Tamkun, M M
AU  - Tamkun MM
FAU - Murray, K T
AU  - Murray KT
LA  - eng
GR  - HL46681/HL/NHLBI NIH HHS/United States
GR  - HL49330/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (KCNA3 protein, human)
RN  - 0 (KCNA5 protein, human)
RN  - 0 (Kv1.3 Potassium Channel)
RN  - 0 (Kv1.5 Potassium Channel)
RN  - 0 (Potassium Channels)
RN  - 0 (Potassium Channels, Voltage-Gated)
RN  - 452VLY9402 (Serine)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
SB  - IM
MH  - Amino Acid Substitution
MH  - Animals
MH  - Cell Line
MH  - Consensus Sequence
MH  - Cyclic AMP-Dependent Protein Kinases/*metabolism
MH  - Enzyme Activation
MH  - Humans
MH  - Kv1.3 Potassium Channel
MH  - Kv1.5 Potassium Channel
MH  - Mutagenesis, Site-Directed
MH  - Oocytes/metabolism
MH  - Phosphorylation
MH  - Potassium Channels/*metabolism
MH  - *Potassium Channels, Voltage-Gated
MH  - Serine/metabolism
MH  - Structure-Activity Relationship
MH  - Xenopus laevis
EDAT- 1999/05/13 02:02
MHDA- 2001/03/28 10:01
CRDT- 1999/05/13 02:02
PHST- 1999/05/13 02:02 [pubmed]
PHST- 2001/03/28 10:01 [medline]
PHST- 1999/05/13 02:02 [entrez]
AID - 10.1074/jbc.274.20.13928 [doi]
AID - S0021-9258(19)73254-2 [pii]
PST - ppublish
SO  - J Biol Chem. 1999 May 14;274(20):13928-32. doi: 10.1074/jbc.274.20.13928.