PIK3CB — Phosphatidylinositol-4,5-bisphosphate 3-kinase Catalytic Subunit Beta

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PIK3CB — Phosphatidylinositol-4,5-bisphosphate 3-kinase Catalytic Subunit Beta

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PIK3CB — Phosphatidylinositol-4,5-bisphosphate 3-kinase Catalytic Subunit Beta

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">pik3cb</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>PIK3CB</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Phosphatidylinositol-4,5-bisphosphate 3-kinase Catalytic Subunit Beta</td>
</tr>
<tr>
<td class="label">Alternative Names</td>
<td>PI3Kβ, p110β</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>22q13.33</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>5293</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000077150</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q14184</td>
</tr>
<tr>
<td class="label">Brain Region</td>
<td>Expression Level</td>
</tr>
<tr>
<td class="label">Cerebral Cortex</td>
<td>High</td>
</tr>
<tr>
<td class="label">Hippocampus</td>
<td>High</td>
</tr>
<tr>
<td class="label">Basal Ganglia</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Cerebellum</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Brainstem</td>
<td>Low-Moderate</td>
</tr>
<tr>
<td class="label">Agent</td>
<td>Type</td>
</tr>
<tr>
<td class="label">AZD8186</td>
<td>PIK3CB inhibitor</td>
</tr>
<tr>
<td class="label">GSK2636771</td>
<td>PIK3CB inhibitor</td>
</tr>
<tr>
<td class="label">PF-04691502</td>
<td>Dual PI3K/mTOR</td>
</tr>

...

PIK3CB — Phosphatidylinositol-4,5-bisphosphate 3-kinase Catalytic Subunit Beta

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">pik3cb</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>PIK3CB</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Phosphatidylinositol-4,5-bisphosphate 3-kinase Catalytic Subunit Beta</td>
</tr>
<tr>
<td class="label">Alternative Names</td>
<td>PI3Kβ, p110β</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>22q13.33</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>5293</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000077150</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q14184</td>
</tr>
<tr>
<td class="label">Brain Region</td>
<td>Expression Level</td>
</tr>
<tr>
<td class="label">Cerebral Cortex</td>
<td>High</td>
</tr>
<tr>
<td class="label">Hippocampus</td>
<td>High</td>
</tr>
<tr>
<td class="label">Basal Ganglia</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Cerebellum</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Brainstem</td>
<td>Low-Moderate</td>
</tr>
<tr>
<td class="label">Agent</td>
<td>Type</td>
</tr>
<tr>
<td class="label">AZD8186</td>
<td>PIK3CB inhibitor</td>
</tr>
<tr>
<td class="label">GSK2636771</td>
<td>PIK3CB inhibitor</td>
</tr>
<tr>
<td class="label">PF-04691502</td>
<td>Dual PI3K/mTOR</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/cancer" style="color:#ef9a9a">Cancer</a>, <a href="/wiki/carcinoma" style="color:#ef9a9a">Carcinoma</a>, <a href="/wiki/cardiac" style="color:#ef9a9a">Cardiac</a>, <a href="/wiki/gastric-cancer" style="color:#ef9a9a">Gastric Cancer</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">70 edges</a></td>
</tr>
</table>

Introduction

PIK3CB encodes the catalytic subunit beta (p110β) 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 that activates AKT (also known as PKB) and downstream signaling cascades. [@franke2007]

PIK3CB is a class IA PI3K catalytic subunit that plays essential roles in:

Signal transduction in response to growth factors, neurotrophins, and cytokines
Neuronal survival through AKT-mediated anti-apoptotic pathways
Synaptic plasticity controlling learning and memory
mTOR signaling regulating protein synthesis and [autophagy](/mechanisms/autophagy)
Cell migration and cytoskeletal reorganization

The PIK3CB isoform has distinct functions from other class I PI3K catalytic subunits (p110α, p110γ, p110δ) and is particularly important in [neuronal function](/cell-types/neurons) and [neurodegenerative diseases](/diseases/alzheimer's-disease). [@yang2014]

Gene Overview

Protein Structure

PIK3CB (p110β) is a ~1048 amino acid protein composed of several functional domains:

N-Terminal Domains

Adapter-Binding Domain (ABD): Mediates interaction with regulatory subunits (p85)
C2 Domain: Binds to lipid membranes and is involved in substrate positioning

Catalytic Core

Helical Domain: Provides structural framework for catalytic activity
Kinase Domain: The catalytic core that transfers phosphate groups from ATP to PIP2

Regulatory Features

p85 Interaction Interface: The N-terminal SH2 domain (nSH2) and inter-SH2 (iSH2) domain of p85 regulatory subunit bind to p110β, regulating its activity
Phosphorylation Sites: Multiple tyrosine and serine/threonine phosphorylation sites regulate activity

The p110β isoform has unique functions compared to p110α:

GPCR coupling: More efficiently coupled to G-protein coupled receptors
RTK signaling: Can be activated by receptor tyrosine kinases independently of p85
Cell type specificity: Higher expression in certain tissues including brain

Normal Physiological Function

PI3K/AKT Signaling Cascade

The PI3K/AKT pathway is a major signaling cascade in neurons:

Receptor Activation: Growth factors (e.g., BDNF, NGF), insulin, or cytokines bind to their cognate receptors

PI3K Activation: Activated receptors recruit PI3K (p85/p110 complex) to the membrane

PIP3 Generation: PIK3CB catalyzes PIP2 → PIP3 conversion

AKT Recruitment: PH domain of AKT binds PIP3 at the membrane

AKT Activation: PDK1 and mTORC2 phosphorylate and activate AKT

Downstream Effects: AKT phosphorylates numerous targets affecting survival, growth, and plasticity

Neuronal Functions

Neuronal Survival

AKT phosphorylates and inhibits pro-apoptotic proteins (Bad, Caspase-9)
Activates NF-κB transcription factor promoting survival genes
Inhibits GSK-3β, reducing tau hyperphosphorylation [@song2012]

Synaptic Plasticity

Modulates NMDA receptor trafficking and function
Regulates AMPA receptor insertion at synapses
Controls local protein synthesis at dendritic spines [@hu2019]

Dendritic Development

Regulates cytoskeletal dynamics through Rac1, Cdc42
Controls dendritic branching and spine morphogenesis
Influences axonal guidance and growth

Autophagy Regulation

mTOR activation by AKT inhibits autophagy
PI3K/AKT/mTOR pathway balances protein synthesis and degradation
Dysregulation contributes to protein aggregate accumulation in neurodegeneration

Cell Type-Specific Functions

Neurons: High expression in cortex, hippocampus, basal ganglia
Astrocytes: Modulates metabolic support and neuroinflammation
Microglia: Regulates inflammatory responses
Oligodendrocytes: Controls myelination and survival

Expression Pattern

PIK3CB is widely expressed throughout the CNS and PNS, with particularly important roles in dopaminergic neurons of the substantia nigra.

Disease Associations

Alzheimer's Disease

PIK3CB is significantly implicated in AD pathogenesis:

Amyloid-beta effects: Aβ reduces PI3K/AKT signaling, contributing to neuronal death. [@barlow2006] Amyloid deposition disrupts the normal PI3K cascade, creating a vicious cycle of neurodegeneration.
Tau phosphorylation: AKT regulates GSK-3β activity, which in turn controls tau hyperphosphorylation. Impaired PI3K/AKT signaling leads to excessive tau pathology. [@song2012]
Synaptic dysfunction: PI3K/AKT is crucial for synaptic plasticity and memory formation. Reduced signaling contributes to cognitive decline. [@hu2019]
Neuronal survival: The neuroprotective effects of PI3K/AKT are compromised in AD, making neurons more vulnerable to apoptotic stimuli. [@cao2009]
Therapeutic implications: Enhancing PI3K/AKT signaling is considered a potential therapeutic strategy for AD. [@kumar2018]

Parkinson's Disease

Dopaminergic neuron survival: PI3K/AKT signaling is critical for survival of dopaminergic neurons in the substantia nigra. Alterations in this pathway contribute to PD pathogenesis.
GWAS associations: Genetic variants near PIK3CB have been implicated in PD risk in genome-wide association studies.
Neuroprotection: PI3K activators have shown promise in protecting dopaminergic neurons in preclinical models.
α-Synuclein pathology: PI3K/AKT signaling may be affected by α-synuclein aggregation, though the relationship is complex.

Amyotrophic Lateral Sclerosis (ALS)

Motor neuron survival: PI3K/AKT pathway is important for motor neuron survival. Dysregulation occurs in both familial and sporadic ALS.
Growth factor signaling: Impaired signaling in response to neurotrophic factors (BDNF, GDNF) contributes to motor neuron degeneration.
mTOR dysregulation: Altered mTOR signaling affects autophagy, potentially leading to accumulation of toxic protein aggregates.
Energy metabolism: PI3K/AKT regulates cellular energy metabolism, which is perturbed in ALS.

Other Neurological Conditions

Stroke/ischemia: PI3K/AKT mediates neuroprotective effects of preconditioning and growth factors
Traumatic brain injury: Enhanced PI3K signaling promotes recovery
Epilepsy: Altered PI3K signaling affects neuronal excitability
Intellectual disability: PI3K signaling crucial for neurodevelopment

Cancer (Non-Neural Context)

While not the focus of NeuroWiki, PIK3CB has important roles in cancer:

PTEN-deficient cancers: When PTEN (negative regulator of PI3K) is lost, cancers become dependent on PIK3CB. [@hollander2011]
Glioblastoma: PIK3CB promotes survival of glioblastoma cells. [@winkler2017]
Resistance to therapy: PIK3CB can confer resistance to PI3Kα inhibitors. [@jia2016]

Signaling Pathway

Mermaid diagram (expand to render)

Therapeutic Implications

Drug Development

PIK3CB is a therapeutic target in multiple contexts:

Challenges in Neurology

Blood-brain barrier: Achieving sufficient brain penetration remains challenging

Isoform selectivity: Developing selective PIK3CB inhibitors vs. other isoforms

Dose optimization: Balancing efficacy with metabolic side effects

Timing: Optimal intervention point in disease progression

Combination therapy: Synergy with other AD/PD therapeutics

Potential Strategies

PI3K activators: Small molecules that enhance PI3K/AKT signaling
AKT agonists: Direct AKT activators bypassing PI3K
mTOR modulators: Adjusting the downstream balance between synthesis and autophagy
Neurotrophic factors: BDNF or GDNF mimetics that activate PI3K

Research Directions

Ongoing Areas of Investigation

Isoform-specific functions: Understanding distinct roles of p110β vs. other class I PI3Ks in neurons

GPCR coupling: PIK3CB's role in mediating neurotransmitter effects

Subcellular localization: PI3K signaling microdomains in neurons

Optogenetics: Light-controlled PI3K signaling probes

Biomarkers: PIP3/AKT pathway activity markers in CSF

Key Unanswered Questions

What are the precise molecular mechanisms by which PIK3CB loss contributes to neurodegeneration?
Can selective PIK3CB modulation provide neuroprotection without cancer risk?
What is the optimal timing for intervention in AD/PD progression?
How do different neuronal cell types depend on PIK3CB signaling?

References

[Song et al., PI3K/Akt signaling in Alzheimer's disease (2012)](https://pubmed.ncbi.nlm.nih.gov/22820262/)

[Franke, PI3K/Akt: getting it right matters (2007)](https://pubmed.ncbi.nlm.nih.gov/17631422/)

[Brachmann et al., Phosphoinositide 3-kinase signaling in neuronal development (2005)](https://pubmed.ncbi.nlm.nih.gov/15632202/)

[Barlow et al., PI3K in Alzheimer's disease amyloid metabolism (2006)](https://pubmed.ncbi.nlm.nih.gov/16469116/)

[Cao et al., PI3K/Akt signaling in neuroprotection and neuronal death (2009)](https://pubmed.ncbi.nlm.nih.gov/19130911/)

[Yang et al., Class I PI3K isoforms in neuronal development (2014)](https://pubmed.ncbi.nlm.nih.gov/24285122/)

[Miller et al., Phosphoinositide 3-kinase in brain disease (2011)](https://pubmed.ncbi.nlm.nih.gov/21466015/)

[Friessel et al., PIK3CB promotes oesophageal cancer proliferation (2024)](https://pubmed.ncbi.nlm.nih.gov/35842767/)

[Lee et al., PI3K beta in cancer biology and therapy (2022)](https://pubmed.ncbi.nlm.nih.gov/35780638/)

[Jia et al., PIK3CB confers resistance to PI3K inhibition (2016)](https://pubmed.ncbi.nlm.nih.gov/26759240/)

[Hollander et al., PTEN-deficient cancers depend on PIK3CB (2011)](https://pubmed.ncbi.nlm.nih.gov/21258771/)

[Winkler et al., PI3Kβ is required for glioblastoma cell survival (2017)](https://pubmed.ncbi.nlm.nih.gov/29016844/)

[Thornton et al., The role of PI3Kβ in neuronal signaling (2016)](https://pubmed.ncbi.nlm.nih.gov/)

[Hu et al., PI3K/AKT pathway in synaptic plasticity and memory (2019)](https://pubmed.ncbi.nlm.nih.gov/)

[Kumar et al., Targeting PI3K signaling in Alzheimer's disease (2018)](https://pubmed.ncbi.nlm.nih.gov/)

Pathway Diagram

The following diagram shows the key molecular relationships involving PIK3CB — Phosphatidylinositol-4,5-bisphosphate 3-kinase Catalytic Subunit Beta discovered through SciDEX knowledge graph analysis:

Mermaid diagram (expand to render)

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Related Entities

PIK3CB

▸Metadataorigin_type: v1_polymorphic_backfill

slug	genes-pik3cb
kg_node_id	PIK3CB
entity_type	gene
origin_type	v1_polymorphic_backfill
source_table	wiki_pages
wiki_page_id	wp-2e405f8877c8
__merged_from	{'merged_at': '2026-05-13', 'unprefixed_id': 'genes-pik3cb'}
_schema_version	1

📊 Evidence Profile

Evidence Balance

+0%

Certainty

35%

Debates

0

Incoming

7

Outgoing

27

0 supporting 0 contradicting 0 neutral

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📗 Cite This Artifact

PIK3CB — Phosphatidylinositol-4,5-bisphosphate 3-kinase Catalytic Subunit Beta

PIK3CB — Phosphatidylinositol-4,5-bisphosphate 3-kinase Catalytic Subunit Beta

PIK3CB — Phosphatidylinositol-4,5-bisphosphate 3-kinase Catalytic Subunit Beta

Introduction

Gene Overview

Protein Structure

N-Terminal Domains

Catalytic Core

Regulatory Features

Normal Physiological Function

PI3K/AKT Signaling Cascade

Neuronal Functions

Cell Type-Specific Functions

Expression Pattern

Disease Associations

Alzheimer's Disease

Parkinson's Disease

Amyotrophic Lateral Sclerosis (ALS)

Other Neurological Conditions

Cancer (Non-Neural Context)

Signaling Pathway

Therapeutic Implications

Drug Development

Challenges in Neurology

Potential Strategies

Research Directions

Ongoing Areas of Investigation

Key Unanswered Questions

See Also

References

Pathway Diagram

💬 Discussion