Functional Diversity of Protein Phosphatase-1, a Cellular Economizer and Reset Button

Abstract

Ceulemans, Hugo, and Mathieu Bollen. Functional Diversity of Protein Phosphatase-1, a Cellular Economizer and Reset Button. Physiol Rev 84: 1–39, 2004; 10.1152/physrev.00013.2003.—The protein serine/threonine phosphatase protein phosphatase-1 (PP1) is a ubiquitous eukaryotic enzyme that regulates a variety of cellular processes through the dephosphorylation of dozens of substrates. This multifunctionality of PP1 relies on its association with a host of function-specific targetting and substrate-specifying proteins. In this review we discuss how PP1 affects the biochemistry and physiology of eukaryotic cells. The picture of PP1 that emerges from this analysis is that of a “green” enzyme that promotes the rational use of energy, the recycling of protein factors, and a reversal of the cell to a basal and/or energy-conserving state. Thus PP1 promotes a shift to the more energy-efficient fuels when nutrients are abundant and stimulates the storage of energy in the form of glycogen. PP1 also enables the relaxation of actomyosin fibers, the return to basal patterns of protein synthesis, and the recycling of transcription and splicing factors. In addition, PP1 plays a key role in the recovery from stress but promotes apoptosis when cells are damaged beyond repair. Furthermore, PP1 downregulates ion pumps and transporters in various tissues and ion channels that are involved in the excitation of neurons. Finally, PP1 promotes the exit from mitosis and maintains cells in the G1or G2phases of the cell cycle.

The protein phosphatase-1/inhibitor-2 complex differentially regulates GSK3 dephosphorylation and increases sarcoplasmic/endoplasmic reticulum calcium ATPase 2 levels

“…Previously, both GSK3β [32] and PP1 [5] were shown to regulate the expression and activity of SERCA2, respectively. Therefore, we tested if the inhibition of GSK3 pharmacologically or through the inhibition of PP1 with I-2 would affect SERCA2 levels in SH-SY5Y cells.…”

Functional characterization of Fusarium verticillioides CPP1, a gene encoding a putative protein phosphatase 2A catalytic subunit

“…While protein kinases take part in phosphorylation, protein phosphatases catalyse the dephosphorylation of proteins, thereby exerting a fundamental role in regulating cellular processes (Dickman & Yarden, 1999). It has been suggested that about one-third of the eukaryotic proteins are regulated by reversible phosphorylations of specific serine, threonine and/or tyrosine residues (Ceulemans & Bollen, 2004). To date, the major group of serine/threonine protein phosphatases are encompassed by two different structural families.…”

“…Protein phosphatases catalyse the dephosphorylation of specific substrates that are important for processing various biological and cellular functions (Ceulemans & Bollen, 2004;Dickman & Yarden, 1999;Hunter, 1995), and this catalytic action is known to de-activate signalling pathways induced by a variety of protein kinases (Hunter, 1995). In Arabidopsis, for instance, protein phosphatase type 2C is involved in the negative regulation of the abscisic acid signalling pathway (Saez et al, 2004).…”

Regulation of human DNA polymerase delta in the cellular responses to DNA damage

“…p68 possesses a variant of the RVXF motif by which PP1 binds to its various targeting subunits [Zhao and Lee, 1997]. The actions of PP1 are restricted to the vicinity of its microenvironment, so that its cellular functions are dictated by its localization via these targeting subunits [Barford et al, 1998;Ceulemans and Bollen, 2004]. This argues that binding of PP1 to p68 functions to regulate phosphorylation states of Pol d itself or of its neighbors within the replication machinery.…”