Protein phosphatase regulation by endogenous inhibitors.
Activation and inactivation of protein kinases and phosphatases trigger key events in the eukaryotic cell division cycle. Coordinating the opposing actions of kinases and phosphatases is also crucial for determining the cellular response to physiological stimuli. While regulatory subunits can control the subcellular localization and substrate specificity of protein phosphatases, endogenous inhibitors represent a mechanism for regulating the overall activity of specific enzymes in mammalian tissues. Some phosphatase inhibitors are phosphoproteins. Therefore, they communicate changes in kinase activity to selected phosphatases. This crosstalk between kinases and phosphatases defines the physiological response. Current knowledge on the mode of action of phosphatase inhibitors and their potential contributions to cell growth and differentiation are discussed.
Shenolikar
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Department of Pharmacology, Duke University Medical Center, Durham, NC 27708, USA.
D000818:Animals; D002352:Carrier Proteins; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D004722:Endoribonucleases; D004791:Enzyme Inhibitors / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors*; D010750:Phosphoproteins / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000378:metabolism; D016601:RNA-Binding Proteins
D002352:Carrier Proteins; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D011506:Proteins; D016601:RNA-Binding Proteins; C021042:protein phosphatase inhibitor-1; D004722:Endoribonucleases; D010749:Phosphoprotein Phosphatases; C097081:PPP1R8 protein, human