Protein Phosphatase 1
Protein serine/threonine phosphatase

Author: Elisa Bellini
Date: 22/02/2012


Elisa Bellini
Elisa Caligaris


Protein Phosphatase 1(PP1) is a member of Ser/Thr phosphatase family and is ubiquitously expressed in all eukaryotic cells. PP1 figures prominently in a wide range of cellular processes, including meiosis and cell division, apoptosis, protein synthesis, metabolism, cytoskeletal reorganization, and the regulation of membrane receptors and channels.


Each functional PP1 enzyme consists of a catalytic subunit and a regulatory subunit (R subunit )These R subunits may target the PP1 catalytic subunit to specific subcellular compartment, modulate substrate specificity, or serve as substrates themselves. Thus, the interactions between the catalytic subunit and specific R subunits are central to the functions of PP1.
The catalytic subunit consists of a 30-kD single-domain protein that can form complexes with other regulatory subunits The catalytic subunit of PP1 adopts a compact α/β fold, with a β sandwich wedged between two α-helical domains.The interaction of the three β-sheets of the β-sandwich creates a channel for catalytic activity, as it is the site of coordination of metal ions. These metal ions have been identified as Mn2+and Fe2+ and their coordination is provided by three histidines, two aspartic acids, and one asparagine.

The two metal ions are thought to bind and activate a water molecule, which initiates a nucleophilic attack on the phosphorous atom The diverse forms of protein phosphatase 1 in vivo result from the association of its catalytic subunit (PP1c) with different regulatory subunits, one of which is the G-subunit (GM) that targets PP1c to glycogen particles in muscle.


The glycogen-associated form of PP1 (PP1c) is a heterodimer composed of the PP1 catalytic © subunit complexed to a 161-kDa glycogen-binding (G) subunitresponsible for association with glycogen.
The residues in GM[63–75] that interact with PP1c are those in the Arg/Lys–Val/Ile– Xaa–Phe motif that is present in almost every other identified mammalian PP1-binding subunit.
PPlc has the same activitays the free C-subunit toward substrates which do not interact with ghlycogen such as myosin light chains.These findings have introduced the concept of targeting subunits as a mechanism for directing PPI to particular subcellular locationsand for selectively enhancing activity toward certain substrates.They also indicate that PP1c plays a major role in the regulation of glycogen metabolism.
PP1 is important to the reciprocal regulation of glycogen metabolism by ensuring the opposite regulation of glycogen breakdown and glycogen synthesis.

The insuline triggers the activation of PP1 indirectly, but the mechanism in not complitly known.
Phosphorylation of GM by PKA in response to adrenaline triggers dissociation of PP1c from GM and thus inactivation of PP1c towards the glycogen-bound substrates, phosphorylase, phosphorylase kinase and glycogen synthase.


The Ca2+/calmodulin-regulated myosin light chain kinase (MLCK) mediates smooth muscle contraction in response to a rise in intracellular Ca2+ levels by phosphorylating the myosin P-light chains at Ser19. Dephosphorylation is catalysed by a trimeric complex containing PP1c with M110 and M21, causing smooth muscle relaxation


January 15, 2002 J Cell Sci 115, 241-256.

EMBO J. 1997 April 15; 16(8): 1876–1887.

doi: 10.1093/emboj/16.8.1876

THE JOURNAL OF BIOLOGICACLH EMISTRY Vol. 264 No. 36 Issue of December 25, pp. 21435-21438.

Cell Volume 139, Issue 3, 30 October 2009, Pages 468–484

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