Please use this identifier to cite or link to this item:
|Title:||Phenylephrine promotes phosphorylation of bad in cardiac myocytes through the extracellular signal-regulated kinases 1/2 and protein kinase A||Authors:||Valks D.M.
Mitogen-activated protein kinases
|Issue Date:||2002||Publisher:||Academic Press||Citation:||Valks D.M., Cook S.A., Pham F.H., Morrison P.R., Clerk A., Sugden P.H. (2002). Phenylephrine promotes phosphorylation of bad in cardiac myocytes through the extracellular signal-regulated kinases 1/2 and protein kinase A. Journal of Molecular and Cellular Cardiology 34 (7) : 749-763. ScholarBank@NUS Repository. https://doi.org/10.1006/jmcc.2002.2014||Abstract:||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 �M) and the cell membrane-permeating cAMP analog, 8-(4-chlorophenylthio)-cAMP (100 �M), 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 ?-adrenoceptor, but, at high concentrations (100 �M), it also increases the activity of the cAMP-dependent protein kinase, protein kinase A (PKA) through the ?-adrenoceptor. Phenylephrine (100 �M) 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 ?1- and ?-adrenoceptors. Phosphorylation of Bad(Ser-155) was antagonized only by propranolol and was thus mediated through the ?-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. � 2002 Elsevier Science Ltd. All rights reserved.||Source Title:||Journal of Molecular and Cellular Cardiology||URI:||http://scholarbank.nus.edu.sg/handle/10635/149286||ISSN:||222828||DOI:||10.1006/jmcc.2002.2014|
|Appears in Collections:||Staff Publications|
Show full item record
Files in This Item:
There are no files associated with this item.
checked on May 15, 2019
WEB OF SCIENCETM
checked on Dec 26, 2018
checked on May 18, 2019
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.