Serine/threonine specific protein phosphatase

Identifiers
EC number	3.1.3.16
CAS number	9001-81-6
Alt. names
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway

Serine/threonine-specific protein phosphatases are a class of enzymes that catalyze the removal of a phosphate group from the amino acids serine and threonine in proteins. This dephosphorylation is a critical regulatory mechanism in many cellular processes, including the cell cycle, apoptosis, and signal transduction pathways.

Structure

Serine/threonine-specific protein phosphatases are typically composed of a catalytic subunit and one or more regulatory subunits. The catalytic subunit is responsible for the enzymatic activity, while the regulatory subunits modulate the activity, specificity, and localization of the phosphatase. The catalytic subunit contains a conserved domain that coordinates metal ions, usually manganese or iron, which are essential for its activity.

Function

The primary function of serine/threonine-specific protein phosphatases is to remove phosphate groups from phosphorylated serine and threonine residues in proteins. This action counteracts the activity of protein kinases, which add phosphate groups to these residues. The balance between phosphorylation by kinases and dephosphorylation by phosphatases is crucial for the regulation of many cellular processes.

Regulation of the Cell Cycle

Serine/threonine-specific protein phosphatases play a vital role in the regulation of the cell cycle. They are involved in the dephosphorylation of key proteins that control the progression through different phases of the cell cycle. For example, protein phosphatase 2A (PP2A) is known to regulate the mitotic spindle assembly and the anaphase-promoting complex.

Signal Transduction

In signal transduction pathways, serine/threonine-specific protein phosphatases modulate the activity of signaling proteins by dephosphorylating them. This can either activate or deactivate the signaling proteins, depending on the context. For instance, protein phosphatase 1 (PP1) is involved in the regulation of glycogen metabolism by dephosphorylating glycogen synthase.

Apoptosis

These phosphatases also have roles in apoptosis, or programmed cell death. They can influence apoptotic pathways by dephosphorylating components of the caspase cascade or other apoptotic regulators.

Types

There are several types of serine/threonine-specific protein phosphatases, each with distinct functions and regulatory mechanisms. The major types include:

• Protein Phosphatase 1 (PP1): Involved in glycogen metabolism, muscle contraction, and cell division.
• Protein Phosphatase 2A (PP2A): Plays a role in cell growth and division, and is a major tumor suppressor.
• Protein Phosphatase 2B (PP2B), also known as calcineurin: Involved in T-cell activation and neuronal signaling.
• Protein Phosphatase 4 (PP4): Involved in DNA repair and cell cycle regulation.

Clinical Significance

Dysregulation of serine/threonine-specific protein phosphatases is associated with various diseases, including cancer, diabetes, and neurodegenerative disorders. For example, mutations in the genes encoding PP2A subunits have been linked to certain types of cancer. Inhibitors of calcineurin, such as cyclosporine and tacrolimus, are used as immunosuppressive drugs in organ transplantation.

Research Directions

Current research on serine/threonine-specific protein phosphatases focuses on understanding their precise roles in cellular processes and their potential as therapeutic targets. Advances in structural biology and genomics are providing new insights into the regulation and function of these enzymes.

See Also

• Protein kinase
• Phosphorylation
• Enzyme regulation

External Links

• UniProt Database
• RCSB Protein Data Bank