PI3K Protein
<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">PI3K Protein</th>
</tr>
<tr>
<td class="label">Gene</td>
<td>[PIK3CA](/genes/PIK3CA) (p110α), [PIK3CB](/genes/PIK3CB) (p110β)</td>
</tr>
<tr>
<td class="label">UniProt</td>
<td><a href="https://www.uniprot.org/uniprot/P42336" target="_blank">P42336</a> (p110α)</td>
</tr>
<tr>
<td class="label">PDB</td>
<td><a href="https://www.rcsb.org/structure/4OVU" target="_blank">4OVU</a>, <a href="https://www.rcsb.org/structure/3ZMS" target="_blank">3ZMS</a></td>
</tr>
<tr>
<td class="label">Mol. Weight</td>
<td>110 kDa (catalytic subunit)</td>
</tr>
<tr>
<td class="label">Localization</td>
<td>Plasma membrane, cytoplasm</td>
</tr>
<tr>
<td class="label">Family</td>
<td>PI3K family, lipid kinases</td>
</tr>
<tr>
<td class="label">Diseases</td>
<td>[Alzheimer's Disease](/diseases/alzheimers), [Parkinson's Disease](/diseases/parkinsons-disease), [Cancer](/diseases/cancer)</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/ad" style="color:#ef9a9a">AD</a>, <a href="/wiki/als" style="color:#ef9a9a">ALS</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">ALZHEIMER</a>, <a href="/wiki/alzheimer's-disease" style="color:#ef9a9a">ALZHEIMER'S DISEASE</a>, <a href="/wiki/ami" style="color:#ef9a9a">AMI</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">3507 edges</a></td>
</tr>
</table>
...PI3K Protein
<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">PI3K Protein</th>
</tr>
<tr>
<td class="label">Gene</td>
<td>[PIK3CA](/genes/PIK3CA) (p110α), [PIK3CB](/genes/PIK3CB) (p110β)</td>
</tr>
<tr>
<td class="label">UniProt</td>
<td><a href="https://www.uniprot.org/uniprot/P42336" target="_blank">P42336</a> (p110α)</td>
</tr>
<tr>
<td class="label">PDB</td>
<td><a href="https://www.rcsb.org/structure/4OVU" target="_blank">4OVU</a>, <a href="https://www.rcsb.org/structure/3ZMS" target="_blank">3ZMS</a></td>
</tr>
<tr>
<td class="label">Mol. Weight</td>
<td>110 kDa (catalytic subunit)</td>
</tr>
<tr>
<td class="label">Localization</td>
<td>Plasma membrane, cytoplasm</td>
</tr>
<tr>
<td class="label">Family</td>
<td>PI3K family, lipid kinases</td>
</tr>
<tr>
<td class="label">Diseases</td>
<td>[Alzheimer's Disease](/diseases/alzheimers), [Parkinson's Disease](/diseases/parkinsons-disease), [Cancer](/diseases/cancer)</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/ad" style="color:#ef9a9a">AD</a>, <a href="/wiki/als" style="color:#ef9a9a">ALS</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">ALZHEIMER</a>, <a href="/wiki/alzheimer's-disease" style="color:#ef9a9a">ALZHEIMER'S DISEASE</a>, <a href="/wiki/ami" style="color:#ef9a9a">AMI</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">3507 edges</a></td>
</tr>
</table>
PI3K Protein
Introduction
Pi3K Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
Overview
PI3K (Phosphoinositide 3-kinase) is a key signaling enzyme that generates phosphatidylinositol (3,4,5)-trisphosphate (PIP3), a critical second messenger that regulates cell survival, growth, proliferation, and metabolism[@cantley2002]. In [neurons](/entities/neurons), PI3K signaling is essential for development, synaptic plasticity, and neuroprotection against various stresses[@th2019].
There are multiple PI3K classes, with Class I PI3Ks being most relevant to signaling:
- Class IA: p110α (PIK3CA), p110β (PIK3CB), p110δ (PIK3CD)
- Class IB: p110γ (PIK3CG)
Each has distinct cellular functions and expression patterns[@zhang2017].
Structure
Class I PI3Ks have a characteristic structure:
Adapter Subunit (p85)
The regulatory subunit contains:
- Two SH2 domains for receptor binding
- SH3 domain for protein interactions
- Inter-SH2 (iSH2) domain for p110 binding
Catalytic Subunit (p110)
The catalytic subunit contains:
- Kinase domain
- C2 domain for membrane association
- Ras-binding domain (RBD)
- Helical domain
Membrane Targeting
PI3K is recruited to the membrane via:
- SH2 domain binding to phosphotyrosines
- Direct binding to activated receptors
- Membrane PIP2 substrate availability[@liu2020]
Normal Function
Signal Transduction
PI3K is activated by:
- Receptor tyrosine kinase activation
- G protein-coupled receptors
- Small GTPases (Ras)
- Integrin signaling
Key Pathways
PI3K activates multiple downstream effectors:
- Akt/PKB: Cell survival, metabolism
- PDK1: Activates Akt
- [mTOR](/mechanisms/mtor-signaling-pathway): Growth, protein synthesis
- GSK-3: Multiple cellular functions
Neuronal Functions
In neurons, PI3K regulates:
- Neurotrophin signaling (Trk receptors)
- Synaptic plasticity ([LTP](/mechanisms/long-term-potentiation), LTD)
- Neuronal survival
- Dendritic spine morphology[^5]
Role in Disease
Alzheimer's Disease
PI3K/Akt signaling is implicated in AD:
- Neurotrophin signaling deficits
- [Tau](/proteins/tau) phosphorylation dysregulation
- [Amyloid-beta](/proteins/amyloid-beta) affects PI3K pathway
- Therapeutic targeting potential
Parkinson's Disease
In PD:
- PI3K protects dopaminergic neurons
- LRRK2 affects PI3K signaling
- Neurotrophin (GDNF) signaling requires PI3K
- PINK1/Parkin pathway connections
Cancer
PI3K is frequently mutated/activated:
- PIK3CA mutations in many cancers
- Oncogenic signaling drives proliferation
- Therapeutic target (PI3K inhibitors)[^6]
Therapeutic Targeting
Therapeutic strategies include:
- PI3K inhibitors: Cancer therapy (idelalisib, alpelisib)
- PI3K activators: Neuroprotective approaches
- Akt activators: Downstream neuroprotection
- mTOR inhibitors: Modulate downstream signaling
- Combined approaches: PI3K + other therapies[^7]
Background
The study of Pi3K Protein has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
Pathway & Interaction Diagram
Interactive diagram showing PI3K's key relationships in the SciDEX knowledge graph (15 connections shown).
Mermaid diagram (expand to render)
See Also
- [Alzheimer's Disease](/diseases/alzheimers-disease)
- [Parkinson's Disease](/diseases/parkinsons-disease)
- [Akt Protein](/proteins/akt-protein)
- [mTOR Protein](/proteins/mtor-protein)
- [Synaptic Plasticity](/mechanisms/synaptic-plasticity)
References
External Links
- [UniProt:-- [Gene: PIK3CA (NCBI)](https://www.ncbi.nlm.nih.gov/gene/5290)