| PIK3CB — Phosphatidylinositol-4,5-bisphosphate 3-kinase Catalytic Subunit Beta |
|---|
| Gene Symbol | PIK3CB |
| Full Name | Phosphatidylinositol-4,5-bisphosphate 3-kinase Catalytic Subunit Beta |
| Chromosomal Location | 22q13.33 |
| NCBI Gene ID | 5293 |
| Ensembl ID | ENSG00000077150 |
| UniProt ID | Q14184 |
| Associated Diseases | Parkinson's Disease, Alzheimer's Disease, ALS |
PIK3CB encodes the catalytic subunit beta of phosphatidylinositol 3-kinase (PI3K), a key enzyme in the PI3K/AKT signaling pathway. PI3K catalyzes the phosphorylation of phosphatidylinositol (4,5)-bisphosphate (PIP2) to generate phosphatidylinositol (3,4,5)-trisphosphate (PIP3), a critical second messenger.
PIK3CB is a class I PI3K catalytic subunit that:
- Generates PIP3 in response to growth factors, neurotrophins, and cytokines
- Activates AKT/PKB — promotes neuronal survival, growth, and plasticity
- Regulates mTOR signaling — controls protein synthesis and autophagy
- Modulates synaptic plasticity — important for learning and memory
- Controls cell migration and cytoskeletal reorganization
PIK3CB variants may modify PD risk:
- GWAS signals near PIK3CB suggest association
- Mechanism: Altered PI3K/AKT signaling affects dopaminergic neuron survival
- Therapeutic target: PI3K inhibitors being explored
PIK3CB is implicated in AD pathogenesis:
- Amyloid-beta effects: Aβ disrupts PI3K/AKT signaling
- Tau phosphorylation: PI3K/AKT regulates tau kinases (GSK3β)
- Neuronal survival: Reduced PI3K signaling contributes to neurodegeneration
PI3K pathway dysregulation in ALS:
- Growth factor signaling impaired in motor neurons
- mTOR hyperactivation affects autophagy
- Therapeutic potential: Modulating PI3K signaling
PIK3CB is widely expressed:
- Brain: Cortex, hippocampus, basal ganglia
- Neurons: Throughout CNS and PNS
- Non-neural: Heart, liver, skeletal muscle
- Song et al., PI3K/AKT in neurodegeneration (2012)
- Franke et al., PI3K in neuronal function (2007)
- Vanhaesebroeck et al., PI3K isoforms in neurological disorders (2010)
- Thacker et al., PI3K signaling in neuronal survival (2006)
- Herrero-Martin et al., PI3K isoform-specific effects in neuronal cells (2015)
- Brachmann et al., PI3K signaling and synaptic plasticity (2005)
- Barlow et al., PI3K in Alzheimer's disease amyloid metabolism (2006)
- Cao et al., PI3K/Akt signaling in neuroprotection (2009)
- Yang et al., Class I PI3K in neuronal development (2014)
- Miller et al., Phosphoinositide 3-kinase in brain disease (2011)