SerinThreoninPhosphatasen

SerinThreoninPhosphatasen, in English serine/threonine phosphatases, are a class of enzymes that remove phosphate groups from serine or threonine residues on proteins. They act in opposition to serine/threonine kinases and are essential for turning off or modulating phosphorylation-dependent signaling pathways. In complex eukaryotic cells their activity is tightly regulated at multiple levels, including subcellular localization, interaction with regulatory subunits, and post-translational modification.

The best characterized groups are the PPP family, which includes PP1, PP2A, PP2B (calcineurin), and PP4–PP7, and the PPM/PP2C family, which are metal-dependent and typically function as monomers. PPP catalytic subunits assemble with regulatory subunits to form holoenzymes with distinct specificities. PP2C enzymes are generally single subunits requiring Mg2+ or Mn2+ for catalysis.

Catalysis relies on metal ions in the active site and conserved motifs. PPP phosphatases show motifs such as GDxHG, GDxVDRG, and GNHE, while PP2C family members have different motifs including DXH. Inhibition or regulation can occur via endogenous proteins, phosphorylation state, or inhibitors such as okadaic acid or microcystin-LR; calcineurin is inhibited by cyclosporine A or tacrolimus via immunophilins.

Physiological roles span signaling pathways including cell cycle control, metabolism, neuronal signaling, and immune responses. For example, calcineurin (PP2B) dephosphorylates NFAT to enable transcription in T cells; PP2A modulates MAP kinase signaling and growth; PP1 participates in glycogen metabolism and spindle function. Dysregulation of serine/threonine phosphatases is linked to cancer, neurodegeneration, and cardiovascular disease.

Research focuses on substrate recognition, regulatory subunit diversity, and development of selective modulators with therapeutic potential. These enzymes are studied with biochemical assays, structural biology, and cellular models to reveal substrate recognition and pathway impacts.