PMID- 12099715
OWN - NLM
STAT- MEDLINE
DCOM- 20030212
LR  - 20220316
IS  - 0022-2828 (Print)
IS  - 0022-2828 (Linking)
VI  - 34
IP  - 7
DP  - 2002 Jul
TI  - Phenylephrine promotes phosphorylation of Bad in cardiac myocytes through the 
      extracellular signal-regulated kinases 1/2 and protein kinase A.
PG  - 749-63
AB  - Studies in non-cardiomyocytic cells have shown that phosphorylation of the Bcl-2 
      family protein Bad on Ser-112, Ser-136 and Ser-155 decreases its pro-apoptotic 
      activity. Both phenylephrine (100 microM) and the cell membrane-permeating cAMP 
      analog, 8-(4-chlorophenylthio)-cAMP (100 microM), protected against 
      2-deoxy-D-glucose-induced apoptosis in neonatal rat cardiac myocytes as assessed 
      by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). 
      In cardiac myocytes, phenylephrine primarily stimulates the alpha-adrenoceptor, 
      but, at high concentrations (100 microM), it also increases the activity of the 
      cAMP-dependent protein kinase, protein kinase A (PKA) through the 
      beta-adrenoceptor. Phenylephrine (100 microM) promoted rapid phosphorylation of 
      Bad(Ser-112) and Bad(Ser-155), though we were unable to detect phosphorylation of 
      Bad(Ser-136). Phosphorylation of Bad(Ser-112) was antagonized by either prazosin 
      or propranolol, indicating that this phosphorylation required stimulation of both 
      alpha(1)- and beta-adrenoceptors. Phosphorylation of Bad(Ser-155) was antagonized 
      only by propranolol and was thus mediated through the beta-adrenoceptor. 
      Inhibitor studies and partial purification of candidate kinases by fast protein 
      liquid chromatography showed that the p90 ribosomal S6 kinases, p90RSK2/3 [which 
      are activated by the extracellular signal-regulated kinases 1 and 2 (ERK1/2)] 
      directly phosphorylated Bad(Ser-112), whereas the PKA catalytic subunit directly 
      phosphorylated Bad(Ser-155). However, efficient phosphorylation of Bad(Ser-112) 
      also required PKA activity. These data suggest that, although p90RSK2/3 
      phosphorylate Bad(Ser-112) directly, phosphorylation of this site is enhanced by 
      phosphorylation of Bad(Ser-155). These phosphorylations potentially diminish the 
      pro-apoptotic activity of Bad and contribute to the cytoprotective effects of 
      phenylephrine and 8-(4-chlorophenylthio)-cAMP.
CI  - Copyright 2002 Elsevier Science Ltd. All rights reserved.
FAU - Valks, Donna M
AU  - Valks DM
AD  - Division of Biomedical Sciences (Cell and Molecular Biology Section), Faculty of 
      Medicine, Imperial College of Science, Technology and Medicine, London, SW7 2AZ, 
      UK.
FAU - Cook, Stuart A
AU  - Cook SA
FAU - Pham, Fong H
AU  - Pham FH
FAU - Morrison, Paul R
AU  - Morrison PR
FAU - Clerk, Angela
AU  - Clerk A
FAU - Sugden, Peter H
AU  - Sugden PH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Mol Cell Cardiol
JT  - Journal of molecular and cellular cardiology
JID - 0262322
RN  - 0 (Bad protein, rat)
RN  - 0 (Carrier Proteins)
RN  - 0 (Receptors, Adrenergic)
RN  - 0 (bcl-Associated Death Protein)
RN  - 1WS297W6MV (Phenylephrine)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
CIN - J Mol Cell Cardiol. 2002 Jul;34(7):709-12. PMID: 12099710
MH  - Animals
MH  - Apoptosis/physiology
MH  - Carrier Proteins/*metabolism
MH  - Cyclic AMP-Dependent Protein Kinases/*metabolism
MH  - Mitogen-Activated Protein Kinases/*metabolism
MH  - Myocytes, Cardiac/drug effects/*metabolism
MH  - Phenylephrine/*pharmacology
MH  - Phosphorylation/drug effects
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Adrenergic/metabolism
MH  - bcl-Associated Death Protein
EDAT- 2002/07/09 10:00
MHDA- 2003/02/14 04:00
CRDT- 2002/07/09 10:00
PHST- 2002/07/09 10:00 [pubmed]
PHST- 2003/02/14 04:00 [medline]
PHST- 2002/07/09 10:00 [entrez]
AID - S0022282802920146 [pii]
AID - 10.1006/jmcc.2002.2014 [doi]
PST - ppublish
SO  - J Mol Cell Cardiol. 2002 Jul;34(7):749-63. doi: 10.1006/jmcc.2002.2014.