PMID- 12594217
OWN - NLM
STAT- MEDLINE
DCOM- 20030716
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 278
IP  - 17
DP  - 2003 Apr 25
TI  - Differential tyrosine phosphorylation of plasma membrane Ca2+-ATPase and 
      regulation of calcium pump activity by carbachol and bradykinin.
PG  - 14872-82
AB  - We investigated the effects of thapsigargin (TG), bradykinin (BK), and carbachol 
      (CCh) on Ca(2+) entry via endogenous channels in human embryonic kidney BKR21 
      cells. After depletion of Ca(2+) stores by either TG, BK, or CCh, the addition of 
      Ca(2+) gave a much larger rise in Ca(2+) levels in CCh-treated and TG-treated 
      cells than in cells treated with BK. However, in experiments performed with 
      Ba(2+), a cation not pumped by Ca(2+)-ATPases, only a modest difference between 
      CCh- and BK-stimulated Ba(2+) entry levels was observed, suggesting that the 
      large difference in the Ca(2+) response is mediated by a differential regulation 
      of Ca(2+) pump activity by CCh and BK. This hypothesis is supported by the 
      finding that when Ca(2+) is removed during the stable, CCh-induced Ca(2+) plateau 
      phase, the decline of cytosolic Ca(2+) is much faster in the absence of CCh than 
      in its presence. In addition, if Ca(2+) is released from a caged Ca(2+) compound 
      after a UV pulse, the resulting Ca(2+) peak is much larger in the presence of CCh 
      than in its absence. Thus, the large increase in Ca(2+) levels observed with CCh 
      results from both the activation of Ca(2+) entry pathways and the inhibition of 
      Ca(2+) pump activity. In contrast, BK has the opposite effect on Ca(2+) pump 
      activity. If Ca(2+) is released from a caged Ca(2+) compound, the resulting 
      Ca(2+) peak is much smaller in the presence of BK than in its absence. An 
      investigation of tyrosine phosphorylation levels of the plasma membrane 
      Ca(2+)-ATPase (PMCA) demonstrated that CCh stimulates an increase in tyrosine 
      phosphorylation levels, which has been reported to inhibit Ca(2+) pump activity, 
      whereas in contrast, BK stimulates a reduction of PMCA tyrosine phosphorylation 
      levels. Thus, BK and CCh have a differential effect both on Ca(2+) pump activity 
      and on tyrosine phosphorylation levels of the PMCA.
FAU - Babnigg, Gyorgy
AU  - Babnigg G
AD  - Department of Neurobiology, Pharmacology, and Physiology, The University of 
      Chicago, Chicago, Illinois 60637, USA.
FAU - Zagranichnaya, Tatiana
AU  - Zagranichnaya T
FAU - Wu, Xiaoyan
AU  - Wu X
FAU - Villereal, Mitchel L
AU  - Villereal ML
LA  - eng
GR  - GM-54500/GM/NIGMS NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20030219
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 42HK56048U (Tyrosine)
RN  - 67526-95-8 (Thapsigargin)
RN  - 8Y164V895Y (Carbachol)
RN  - EC 7.2.2.10 (Calcium-Transporting ATPases)
RN  - S8TIM42R2W (Bradykinin)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Bradykinin/*pharmacology
MH  - Calcium/metabolism
MH  - Calcium-Transporting ATPases/antagonists & inhibitors/*metabolism
MH  - Carbachol/*pharmacology
MH  - Cell Line
MH  - Cell Membrane/enzymology
MH  - Humans
MH  - Kinetics
MH  - Phosphorylation/drug effects
MH  - Thapsigargin/pharmacology
MH  - Tyrosine/*metabolism
EDAT- 2003/02/21 04:00
MHDA- 2003/07/17 05:00
CRDT- 2003/02/21 04:00
PHST- 2003/02/21 04:00 [pubmed]
PHST- 2003/07/17 05:00 [medline]
PHST- 2003/02/21 04:00 [entrez]
AID - S0021-9258(19)30284-4 [pii]
AID - 10.1074/jbc.M210418200 [doi]
PST - ppublish
SO  - J Biol Chem. 2003 Apr 25;278(17):14872-82. doi: 10.1074/jbc.M210418200. Epub 2003 
      Feb 19.