PPP2R2A (Protein Phosphatase 2 Regulatory Subunit B55 Alpha) encodes the B55α regulatory subunit of protein phosphatase 2A (PP2A), one of the most abundant serine/threonine phosphatases in the brain. Located at chromosome 8p21.2, PPP2R2A is essential for targeting PP2A catalytic activity to specific substrates, including the microtubule-associated protein tau 1.
Dysregulation of PPP2R2A and resulting PP2A dysfunction is a hallmark of Alzheimer's disease and other neurodegenerative disorders, making it a critical therapeutic target 2.
| Feature | Value |
|---|---|
| Gene Symbol | PPP2R2A |
| Full Name | Protein Phosphatase 2 Regulatory Subunit B55 Alpha |
| Chromosomal Location | 8p21.2 |
| NCBI Gene ID | 5520 |
| OMIM ID | 601728 |
| Ensembl ID | ENSG00000156535 |
| UniProt ID | P63151 |
| Protein Length | 447 amino acids |
| Molecular Weight | ~52 kDa |
PPP2R2A encodes the B55α (also known as PR55α) regulatory subunit that forms the PP2A-B55α holoenzyme with:
This trimeric complex is the predominant form of PP2A in neurons and is specifically enriched at synapses 3.
The B55α subunit directs PP2A to dephosphorylate key neuronal substrates:
| Substrate | Site | Relevance |
|---|---|---|
| Tau | Ser202, Thr205, Ser396 | NFT formation |
| APP | Thr668 | Amyloid processing |
| Synapsin I | Ser9 | Synaptic plasticity |
| NMDA Receptor | Ser1323 | Excitotoxicity |
PP2A-B55α is the primary tau phosphatase in the brain, responsible for:
In AD brain, PP2A-B55α activity is reduced by 30-50%, contributing to tau hyperphosphorylation 4.
PP2A-B55α regulates synaptic plasticity through:
The phosphatase complex regulates:
PP2A-B55α activity protects neurons by:
PPP2R2A dysfunction in AD involves multiple mechanisms:
In PD, PP2A-B55α affects:
PPP2R2A has complex roles in cancer:
Several compounds are being developed to activate PP2A-B55α:
| Compound | Mechanism | Status |
|---|---|---|
| ABT-737 | Inhibits SET/I2PP2A | Preclinical |
| FTY720 (Fingolimod) | Multiple mechanisms | Clinical trials |
| Saluben | Direct B55α interaction | Research |
PP2A activation represents a direct approach to:
PPP2R2A-related measurements may serve as:
PPP2R2A participates in key signaling pathways: