Andrew J. Murray
Jun 3, 2008
Citations
30
Influential Citations
328
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Quality indicators
Journal
Science Signaling
Abstract
Signaling through the cyclic adenosine monophosphate–dependent protein kinase [protein kinase A (PKA)] is an important and widely studied area of signal transduction research. This signaling pathway is commonly investigated through the use of the pharmacological PKA inhibitors H89 and KT 5720. Both of these compounds are thought to block PKA actions through competitive inhibition of the adenosine triphosphate site on the PKA catalytic subunit. Recently, a number of studies have identified actions of H89 and KT 5720 that are independent of their effects on PKA. These nonspecific effects are widespread; they include actions on other protein kinases and signaling molecules and also on basic cellular functions, such as transcription. Here, I summarize the nonspecific effects of these two compounds and compare their actions with those of other PKA inhibitors. One of the ways in which cells transduce intracellular signals is through the reversible phosphorylation of proteins by enzymes called protein kinases. Protein kinase A (PKA) is one of these kinases; it is activated in response to increases in intracellular cyclic adenosine monophosphate (cAMP) production and is involved in numerous cellular processes, including exocytosis, cell migration, and regulation of gene transcription. Many of the studies that have examined PKA function in cells have used two pharmacological PKA inhibitors, H89 and KT 5720. Recently, a number of studies have identified actions of these compounds that are not related to their ability to block PKA. This may cast doubt onto some of the accepted functions of PKA in cells, which were established in experiments using these inhibitors. Here, I discuss the nonspecific actions of H89 and KT 5720 and compare their actions to those of other PKA inhibitors.