Functional regulation of L-type calcium channels via protein kinase
A-mediated phosphorylation of the beta(2) subunit
M. Bunemann, B. Gerhardstein, T. Gao, и M. Hosey. J Biol Chem, 274 (48):
33851-4(ноября 1999)Bunemann, M Gerhardstein, B L Gao, T Hosey, M M HL23306/HL/NHLBI
NIH HHS/United States T32-DK07169/DK/NIDDK NIH HHS/United States
Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.
United states The Journal of biological chemistry J Biol Chem. 1999
Nov 26;274(48):33851-4..
Аннотация
Activation of protein kinase A (PKA) through the beta-adrenergic receptor
pathway is crucial for the positive regulation of cardiac L-type
currents; however it is still unclear which phosphorylation events
cause the robust regulation of channel function. In order to study
whether or not the recently identified PKA phosphorylation sites
on the beta(2) subunit are of functional significance, we coexpressed
wild-type (WT) or mutant beta(2) subunits in tsA-201 cells together
with an alpha(1C) subunit, alpha(1C)Delta1905, that lacked the C-terminal
265 amino acids, including the only identified PKA site at Ser-1928.
This truncated alpha(1C) subunit was similar to the truncated alpha(1C)
subunit isolated from cardiac tissue not only in size ( approximately
190 kDa), but also with respect to its failure to serve as a PKA
substrate. In cells transfected with the WT beta(2) subunit, voltage-activated
Ba(2+) currents were significantly increased when purified PKA was
included in the patch pipette. Furthermore, mutations of Ser-478
and Ser-479 to Ala, but not Ser-459 to Ala, on the beta(2) subunit,
completely abolished the PKA-induced increase of currents. The data
indicate that the PKA-mediated stimulation of cardiac L-type Ca(2+)
currents may be at least partially caused by phosphorylation of the
beta(2) subunit at Ser-478 and Ser-479.
Bunemann, M Gerhardstein, B L Gao, T Hosey, M M HL23306/HL/NHLBI
NIH HHS/United States T32-DK07169/DK/NIDDK NIH HHS/United States
Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.
United states The Journal of biological chemistry J Biol Chem. 1999
Nov 26;274(48):33851-4.
%0 Journal Article
%1 Bunemann1999
%A Bunemann, M.
%A Gerhardstein, B. L.
%A Gao, T.
%A Hosey, M. M.
%D 1999
%J J Biol Chem
%K AMP-Dependent Animals Barium Calcium Cell Channels, Chlorides/pharmacology Compounds/pharmacology Cyclic Electric Fusion Humans Kinases/*pharmacology L-Type/chemistry/genetics/*metabolism Line, Membrane Patch-Clamp Phosphorylation/drug Potentials/drug Protein Proteins/genetics/metabolism Rabbits Rats Recombinant Serine/metabolism Stimulation Techniques Transformed effects
%N 48
%P 33851-4
%T Functional regulation of L-type calcium channels via protein kinase
A-mediated phosphorylation of the beta(2) subunit
%U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10567342
%V 274
%X Activation of protein kinase A (PKA) through the beta-adrenergic receptor
pathway is crucial for the positive regulation of cardiac L-type
currents; however it is still unclear which phosphorylation events
cause the robust regulation of channel function. In order to study
whether or not the recently identified PKA phosphorylation sites
on the beta(2) subunit are of functional significance, we coexpressed
wild-type (WT) or mutant beta(2) subunits in tsA-201 cells together
with an alpha(1C) subunit, alpha(1C)Delta1905, that lacked the C-terminal
265 amino acids, including the only identified PKA site at Ser-1928.
This truncated alpha(1C) subunit was similar to the truncated alpha(1C)
subunit isolated from cardiac tissue not only in size ( approximately
190 kDa), but also with respect to its failure to serve as a PKA
substrate. In cells transfected with the WT beta(2) subunit, voltage-activated
Ba(2+) currents were significantly increased when purified PKA was
included in the patch pipette. Furthermore, mutations of Ser-478
and Ser-479 to Ala, but not Ser-459 to Ala, on the beta(2) subunit,
completely abolished the PKA-induced increase of currents. The data
indicate that the PKA-mediated stimulation of cardiac L-type Ca(2+)
currents may be at least partially caused by phosphorylation of the
beta(2) subunit at Ser-478 and Ser-479.
@article{Bunemann1999,
abstract = {Activation of protein kinase A (PKA) through the beta-adrenergic receptor
pathway is crucial for the positive regulation of cardiac L-type
currents; however it is still unclear which phosphorylation events
cause the robust regulation of channel function. In order to study
whether or not the recently identified PKA phosphorylation sites
on the beta(2) subunit are of functional significance, we coexpressed
wild-type (WT) or mutant beta(2) subunits in tsA-201 cells together
with an alpha(1C) subunit, alpha(1C)Delta1905, that lacked the C-terminal
265 amino acids, including the only identified PKA site at Ser-1928.
This truncated alpha(1C) subunit was similar to the truncated alpha(1C)
subunit isolated from cardiac tissue not only in size ( approximately
190 kDa), but also with respect to its failure to serve as a PKA
substrate. In cells transfected with the WT beta(2) subunit, voltage-activated
Ba(2+) currents were significantly increased when purified PKA was
included in the patch pipette. Furthermore, mutations of Ser-478
and Ser-479 to Ala, but not Ser-459 to Ala, on the beta(2) subunit,
completely abolished the PKA-induced increase of currents. The data
indicate that the PKA-mediated stimulation of cardiac L-type Ca(2+)
currents may be at least partially caused by phosphorylation of the
beta(2) subunit at Ser-478 and Ser-479.},
added-at = {2010-12-14T18:12:02.000+0100},
author = {Bunemann, M. and Gerhardstein, B. L. and Gao, T. and Hosey, M. M.},
biburl = {https://www.bibsonomy.org/bibtex/2d14d2beeb5da0c9e1c3ae02276cfeece/pharmawuerz},
endnotereftype = {Journal Article},
interhash = {2a55134f0ad957660a126cf260179fa9},
intrahash = {d14d2beeb5da0c9e1c3ae02276cfeece},
issn = {0021-9258 (Print) 0021-9258 (Linking)},
journal = {J Biol Chem},
keywords = {AMP-Dependent Animals Barium Calcium Cell Channels, Chlorides/pharmacology Compounds/pharmacology Cyclic Electric Fusion Humans Kinases/*pharmacology L-Type/chemistry/genetics/*metabolism Line, Membrane Patch-Clamp Phosphorylation/drug Potentials/drug Protein Proteins/genetics/metabolism Rabbits Rats Recombinant Serine/metabolism Stimulation Techniques Transformed effects},
month = {Nov 26},
note = {Bunemann, M Gerhardstein, B L Gao, T Hosey, M M HL23306/HL/NHLBI
NIH HHS/United States T32-DK07169/DK/NIDDK NIH HHS/United States
Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.
United states The Journal of biological chemistry J Biol Chem. 1999
Nov 26;274(48):33851-4.},
number = 48,
pages = {33851-4},
shorttitle = {Functional regulation of L-type calcium channels via protein kinase
A-mediated phosphorylation of the beta(2) subunit},
timestamp = {2010-12-14T18:12:06.000+0100},
title = {Functional regulation of L-type calcium channels via protein kinase
A-mediated phosphorylation of the beta(2) subunit},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10567342},
volume = 274,
year = 1999
}