Protein phosphatase 1--targeted in many directions.
Protein phosphatase 1 (PP1) is a major eukaryotic protein serine/threonine phosphatase that regulates an enormous variety of cellular functions through the interaction of its catalytic subunit (PP1c) with over fifty different established or putative regulatory subunits. Most of these target PP1c to specific subcellular locations and interact with a small hydrophobic groove on the surface of PP1c through a short conserved binding motif--the RVxF motif--which is often preceded by further basic residues. Weaker interactions may subsequently enhance binding and modulate PP1 activity/specificity in a variety of ways. Several putative targeting subunits do not possess an RVxF motif but nevertheless interact with the same region of PP1c. In addition, several 'modulator' proteins bind to PP1c but do not possess a domain targeting them to a specific location. Most are potent inhibitors of PP1c and possess at least two sites for interaction with PP1c, one of which is identical or similar to the RVxF motif. Regulation of PP1c in response to extracellular and intracellular signals occurs mostly through changes in the levels, conformation or phosphorylation status of targeting subunits. Understanding of the mode of action of PP1c complexes may facilitate development of drugs that target particular PP1c complexes and thereby modulate the phosphorylation state of a very limited subset of proteins.
Cohen
Patricia T W
PT
Medical Research Council Protein Phosphorylation Unit, School of Life Sciences, University of Dundee, Dundee DD15EH, Scotland, UK. p.t.w.cohen@dundee.ac.uk
D000818:Animals; D001665:Binding Sites / Q000502:physiology; D020134:Catalytic Domain / Q000502:physiology*; D006801:Humans; D008968:Molecular Conformation; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D054645:Protein Phosphatase 1; D015398:Signal Transduction / Q000502:physiology*; D014780:Viruses / Q000378:metabolism
D020033:Protein Isoforms; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1