Phosphatases Flashcards
What is the role of Protein Phosphatase 1?
Muscle contraction, glycogen metabolism, and cell division.
What is the role of Protein Phosphate 2 A?
PP2A plays a key role in the regulation of cell growth and division, and it is involved in the control of various signaling pathways. It is a heterotrimeric enzyme composed of a catalytic subunit, a scaffolding subunit, and a regulatory subunit. The regulatory subunits confer substrate specificity and subcellular localization.
What is the role of Protein Phosphate 2B?
PP2B is a calcium/calmodulin-dependent phosphatase involved in the regulation of T-cell activation and other calcium-mediated signaling pathways. It is activated by the binding of calcium ions and calmodulin.
What is the role of Protein Phosphatase 2C?
PP2C enzymes are involved in stress response pathways and metabolic control. They are monomeric enzymes that require magnesium or manganese ions for their activity.
What is the role of PP4, 5, 6?
DNA damage repair (PP4)
Signal transduction (PP5)
Cell cycle regulation (PP6)
Mechanism of action of calcineurin:
Calcineurin is a serine/threonine phosphatase that plays a crucial role in activating T-cells. It does this by dephosphorylating the Nuclear Factor of Activated T-cells (NF-AT), which allows NF-AT to enter the nucleus and start the transcription of interleukin-2 (IL-2), a key factor for T-cell proliferation.
Effect of immunosuppressants Cyclosporin and FK506:
Cyclosporin and FK506 are immunosuppressive drugs used mainly in transplantations. They target calcineurin by forming complexes with cyclophilin or FKBP. These complexes inhibit calcineurin’s activity, which in turn inhibits IL-2 transcription and reduces T-cell proliferation. This mechanism effectively modulates the immune response, preventing organ rejection.
Inhibition of tyrosine phosphatase by vanadate:
Vanadate acts as a phosphate analog. It mimics the phosphorylated tyrosine residue and binds to the active site of the phosphatase. This competitive inhibition prevents the actual substrate from accessing the active site, thereby inhibiting the dephosphorylation process.
Inhibition of tyrosine phosphatase by arsenoxide:
Arsenoxide acts as a phosphate analog. By mimicking the phosphorylated state, it inhibits the nucleophilic attack by the cysteine thiolate on the actual phosphorylated protein, effectively blocking the phosphatase activity.
What are the two classes of tyrosine phosphatases?
- Receptor-like (transmembrane) phosphatases are involved involved in extracellular signaling and cell-cell interactions (due to their extracellular domain’s interaction capabilities), often having dual catalytic domains.
- Non-transmembrane (cytoplasmic) phosphatases regulate intracellular signaling pathways and have specific domains for interaction and localization.
Tumor suppression by PTEN:
PTEN acts as a critical tumor suppressor by dephosphorylating PIP3 and inhibiting the PI3K/Akt pathway. Its loss leads to uncontrolled cell growth and cancer, making it an important target for cancer therapy and diagnosis.
