[Frontiers in Bioscience 3, d961-972, September 1, 1998]

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Carey J. Oliver and Shirish Shenolikar

Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710

Received 8/14/98 Accepted 8/20/98


This review has focused on the known inhibitor proteins for the major protein serine/threonine phosphatases, PP1 and PP2A, while recognizing that the family of protein phosphatases has continued to expand over the last few years. At this time, there may be more than 200 functionally different serine/threonine phosphatase complexes in mammalian cells. In addition, 100 or more protein tyrosine phosphatases have also been identified. Complete understanding of mechanisms that regulate these enzymes, in many cases, awaits the identification of suitable physiological targets. In this respect, PP1 and PP2A represent the founder members of the protein phosphatase family and have provided us with valuable models for enzyme regulation that could be applied to other phosphatases. Our discussion has attempted to highlight the manner in which phosphatase inhibitors provide for amplification of hormone signals, cross-talk between distinct signal transduction pathways, control the size and duration of a physiological response and act as gatekeepers or decision makers in cell signaling. The presence of many different inhibitors of an individual phosphatase also emphasizes the range of options available to a cell to communicate physiological signals through the protein phosphatase. With the recent expansion in the number of phosphatase catalytic and regulatory subunits, the days of considering protein phosphatases as unregulated or constitutive enzyme activities are finally over.