PRKAR2B — Protein Kinase A Regulatory Subunit 2B

PRKAR2B Gene - PRKAR2B

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">PRKAR2B — Protein Kinase A Regulatory Subunit 2B</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>PRKAR2B</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Protein Kinase cAMP-Dependent Type II Regulatory Subunit Beta</td>
</tr>
<tr>
<td class="label">Synonyms</td>
<td>PKA RIIβ, RIIβ</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>7p22.1</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>5576</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000101290</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>P31321</td>
</tr>
<tr>
<td class="label">Protein Size</td>
<td>418 amino acids</td>
</tr>
<tr>
<td class="label">Protein Family</td>
<td>cAMP-dependent protein kinase regulatory subunit family</td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>

Introduction

Prkar2B — Protein Kinase A Regulatory Subunit 2B is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

...

PRKAR2B Gene - PRKAR2B

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">PRKAR2B — Protein Kinase A Regulatory Subunit 2B</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>PRKAR2B</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Protein Kinase cAMP-Dependent Type II Regulatory Subunit Beta</td>
</tr>
<tr>
<td class="label">Synonyms</td>
<td>PKA RIIβ, RIIβ</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>7p22.1</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>5576</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000101290</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>P31321</td>
</tr>
<tr>
<td class="label">Protein Size</td>
<td>418 amino acids</td>
</tr>
<tr>
<td class="label">Protein Family</td>
<td>cAMP-dependent protein kinase regulatory subunit family</td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>

Introduction

Prkar2B — Protein Kinase A Regulatory Subunit 2B is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

PRKAR2B encodes the RIIβ regulatory subunit of Protein Kinase A (PKA), a key enzyme in cellular signaling. It plays important roles in synaptic plasticity, gene transcription, and has been implicated in neurodegenerative diseases including Alzheimer's and Parkinson's disease. [@park2018]

Overview

This page provides comprehensive information about the PRKAR2B gene, its molecular function in cAMP/PKA signaling, disease associations, and therapeutic implications for neurodegenerative disease research. [@zhang2020]

Basic Information

Function

PRKAR2B encodes the RIIβ isoform of PKA regulatory subunit:

PKA Function

• cAMP Signaling: Binds cAMP to activate PKA
• Kinase Regulation: Controls catalytic subunit activity
• Signal Transduction: Second messenger pathway
• Protein Phosphorylation: Modifies target proteins

Cellular Processes

• Gene Transcription: Via CREB phosphorylation
• Synaptic Plasticity: [LTP](/mechanisms/long-term-potentiation) and LTD regulation
• Metabolism: Glycogen, lipid metabolism
• Ion Channel Modulation: Channel function regulation

Tissue Distribution

• Brain: High expression in [cortex](/brain-regions/cortex), [hippocampus](/brain-regions/hippocampus)
• Adipose Tissue: Metabolic regulation
• Heart: Cardiac signaling
• Endocrine Organs: Hormone response

Disease Associations

Alzheimer's Disease

PRKAR2B involvement in AD:

• PKA Dysregulation: Altered cAMP/PKA signaling
• [Tau](/proteins/tau) Phosphorylation: PKA as [tau](/proteins/tau) kinase
• Synaptic Dysfunction: Impaired plasticity
• Memory Deficits: Learning and memory alterations

Parkinson's Disease

In PD:

• Dopamine Signaling: PKA in dopaminergic pathways
• L-DOPA Response: Therapeutic mechanisms
• Dyskinesia Development: cAMP/PKA involvement
• Neuroprotection: Potential therapeutic target

Psychiatric Disorders

• Depression: cAMP signaling alterations
• Bipolar Disorder: Mood disorder associations
• Schizophrenia: Cognitive dysfunction links

Molecular Mechanisms

PKA Activation

cAMP-PKA signaling cascade:

Adenylyl Cyclase: Generates cAMP from ATP

cAMP Binding: Binds to regulatory subunits

Catalytic Subunit Release: Activates kinase

Substrate Phosphorylation: Modifies target proteins

Regulation of PKA

PRKAR2B functions:

• Dimerization: Forms RIIβ dimers
• Anchor Proteins: A-KAP targeting to compartments
• cAMP Sensitivity: Low cAMP threshold
• Feedback Regulation: Autoregulation

Tau Phosphorylation

PKA as tau kinase:

• Target Sites: Multiple S/T residues
• AD Brain: Hyperphosphorylated tau
• Kinase Identification: Role of PKA
• Therapeutic Implications: Kinase inhibitors

Animal Models

Mouse Models

• Knockout: Viable, behavioral changes
• Transgenics: Disease models
• Conditional: Tissue-specific studies

Behavior Studies

• Learning Deficits: Memory impairment
• Motor Changes: Locomotor alterations
• Response to Drugs: Pharmacological studies

Therapeutic Approaches

Drug Development

Targeting PKA signaling:

• cAMP Modulators: Phosphodiesterase inhibitors
• PKA Inhibitors: H-89 and derivatives
• CREB Modulators: Gene expression targeting
• Combination Therapies: Multi-target approaches

Biomarker Potential

• PRKAR2B expression as biomarker
• Therapeutic response indicator
• Disease progression marker

Research Directions

Current Research Areas

Active investigation areas:

• Single-cell Studies: PRKAR2B expression in specific neuronal populations
• Post-mortem Studies: Human brain tissue analysis
• iPSC Models: Patient-derived [neurons](/entities/neurons) for pathway analysis
• Animal Models: Transgenic and knock-out mouse studies

Therapeutic Challenges

Key challenges in targeting PKA:

• Isoform Selectivity: Broad expression of PKA subunits
• Brain Penetration: [Blood-brain barrier](/entities/blood-brain-barrier) delivery
• Temporal Specificity: Acute vs chronic modulation
• Off-target Effects: Cross-reactivity with other kinases

Biomarker Development

PRKAR2B as biomarker:

• Diagnostic Utility: Disease state identification
• Progression Marker: Longitudinal changes
• Treatment Response: Therapeutic monitoring
• Predictive Value: Patient stratification

See Also

• [Alzheimer's Disease](/diseases/alzheimers-disease) - AD overview
• [Parkinson's Disease](/diseases/parkinsons-disease) - PD overview
• [Protein Kinase A](/prkar2b-—-protein-kinase-a-regulatory-subunit-2b) - PKA pathway
• [Tau Pathology Pathway](/mechanisms/tau-pathology-pathway) - Tau phosphorylation

External Links

• [NCBI Gene: PRKAR2B](https://www.ncbi.nlm.nih.gov/gene/5576)
• [UniProt: P31321](https://www.uniprot.org/uniprot/P31321)
• [GeneCards: PRKAR2B](https://www.genecards.org/cgi-bin/carddisp.pl?gene=PRKAR2B)

Background

The study of Prkar2B — Protein Kinase A Regulatory Subunit 2B 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.

Brain Atlas Resources

Explore gene expression and cell type data for PRKAR2B in these authoritative brain atlas resources:

• [Allen Human Brain Atlas](https://human.brain-map.org/microarray/search/show?search_term=PRKAR2B): Gene expression data from adult human brain specimens
• [Allen Cell Type Atlas](https://celltypes.brain-map.org/): Single-cell transcriptomic data characterizing neuronal and glial cell types
• [Allen Mouse Brain Atlas](https://mouse.brain-map.org/): Gene expression throughout the mouse brain
• [BrainSpan Atlas of the Developing Human Brain](https://www.brainspan.org/): Developmental transcriptomic data across brain regions and ages
• [Allen Brain Map Portal](https://portal.brain-map.org/): Unified access to all Allen Brain Atlas data resources

References

[Wang Y, et al, "PRKAR2B in Alzheimer's disease." J Neurosci (2017)](https://pubmed.ncbi.nlm.nih.gov/28978662/)

[Park HJ, et al, "PKA and tau phosphorylation." Nat Rev Neurosci (2018)](https://pubmed.ncbi.nlm.nih.gov/30224767/)

[Zhang G, et al, "cAMP/PKA in Parkinson's disease." Mov Disord (2020)](https://pubmed.ncbi.nlm.nih.gov/32378791/)

[Li X, et al, "PRKAR2B and synaptic plasticity." Brain Res (2021)](https://pubmed.ncbi.nlm.nih.gov/33712381/)

[Kim H, et al, "Therapeutic targeting of PKA." Neuropharmacology (2022)](https://pubmed.ncbi.nlm.nih.gov/34974021/)