Protein phosphatase 1

Protein phosphatase 1 (PP1) is a major class of phosphatase enzymes that dephosphorylate serine and threonine residues in proteins. It plays a crucial role in various cellular processes, including cell cycle regulation, glycogen metabolism, muscle contractility, and neuronal signaling. PP1 is highly conserved across eukaryotes, underscoring its importance in cellular physiology.

Structure

PP1 is a holoenzyme composed of a catalytic subunit, PP1c, and regulatory subunits that determine its substrate specificity, subcellular localization, and activity. The catalytic subunit is highly conserved and can associate with over a hundred different regulatory subunits. This diversity allows PP1 to participate in a wide range of cellular functions. The structure of PP1c is characterized by a deep, hydrophobic active site groove where dephosphorylation occurs.

Function

The primary function of PP1 is to remove phosphate groups from serine and threonine residues on proteins. This action can activate or deactivate enzymes and other proteins, thereby regulating their function. PP1 is involved in:

• Glycogen metabolism: PP1 activates glycogen synthase, promoting glycogen synthesis, and inhibits glycogen phosphorylase, decreasing glycogen breakdown.
• Cell cycle control: PP1 dephosphorylates various proteins involved in the cell cycle, ensuring proper cell division and growth.
• Muscle contractility: In muscle cells, PP1 regulates the phosphorylation state of myosin light chains, which influences muscle contraction and relaxation.
• Neuronal signaling: PP1 modulates the activity of neurotransmitter receptors and ion channels, affecting synaptic strength and plasticity.

Regulation

PP1 activity is tightly regulated by its regulatory subunits and by inhibitory proteins such as Inhibitor-1 and DARPP-32. Phosphorylation of these inhibitors can alter their ability to bind PP1c, modulating PP1 activity. Additionally, the localization and substrate specificity of PP1 are governed by its regulatory subunits, which can target PP1 to specific subcellular compartments or substrates.

Clinical Significance

Dysregulation of PP1 has been implicated in several diseases, including cancer, diabetes, and neurodegenerative diseases. For example, altered PP1 activity can lead to aberrant cell growth and division in cancer, or impaired glycogen metabolism in diabetes. Understanding the mechanisms that regulate PP1 and its role in disease may lead to the development of new therapeutic strategies.

See Also

• Phosphatase
• Cell cycle
• Glycogen metabolism
• Neurodegenerative diseases