PMID- 10567342
OWN - NLM
STAT- MEDLINE
DCOM- 19991229
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 48
DP  - 1999 Nov 26
TI  - Functional regulation of L-type calcium channels via protein kinase A-mediated
      phosphorylation of the beta(2) subunit.
PG  - 33851-4
AB  - 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.
FAU - Bunemann, M
AU  - Bunemann M
AD  - Department of Molecular Pharmacology, Northwestern University Medical School,
      Chicago, Illinois 60611, USA.
FAU - Gerhardstein, B L
AU  - Gerhardstein BL
FAU - Gao, T
AU  - Gao T
FAU - Hosey, M M
AU  - Hosey MM
LA  - eng
GR  - HL23306/HL/NHLBI NIH HHS/United States
GR  - T32-DK07169/DK/NIDDK 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 (Barium Compounds)
RN  - 0 (Calcium Channels, L-Type)
RN  - 0 (Chlorides)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0VK51DA1T2 (barium chloride)
RN  - 452VLY9402 (Serine)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
SB  - IM
MH  - Animals
MH  - Barium Compounds/pharmacology
MH  - Calcium Channels, L-Type/chemistry/genetics/*metabolism
MH  - Cell Line, Transformed
MH  - Chlorides/pharmacology
MH  - Cyclic AMP-Dependent Protein Kinases/*pharmacology
MH  - Electric Stimulation
MH  - Humans
MH  - Membrane Potentials/drug effects
MH  - Patch-Clamp Techniques
MH  - Phosphorylation/drug effects
MH  - Rabbits
MH  - Rats
MH  - Recombinant Fusion Proteins/genetics/metabolism
MH  - Serine/metabolism
EDAT- 1999/11/24 00:00
MHDA- 1999/11/24 00:01
CRDT- 1999/11/24 00:00
PHST- 1999/11/24 00:00 [pubmed]
PHST- 1999/11/24 00:01 [medline]
PHST- 1999/11/24 00:00 [entrez]
AID - 10.1074/jbc.274.48.33851 [doi]
AID - S0021-9258(19)53469-X [pii]
PST - ppublish
SO  - J Biol Chem. 1999 Nov 26;274(48):33851-4. doi: 10.1074/jbc.274.48.33851.