PDK3 - 3-Phosphoinositide-Dependent Protein Kinase-3

gene · SciDEX wiki

PDK3 - 3-Phosphoinositide-Dependent Protein Kinase-3
**Symbol** PDK3
**Full Name** 3-Phosphoinositide-Dependent Protein Kinase 3
**Chromosomal Location** Xp22.11
**NCBI Gene ID** 5165
**OMIM ID** 300341
**Ensembl ID** ENSG00000168268
**UniProt ID** O95819
**Protein Size** 350 amino acids
**Molecular Weight** ~39 kDa
Compound Mechanism
**BX-517** PDK1/3 selective inhibitor
**OSU-03012** Multi-PDK inhibitor
**Compound 20** PDK3 selective
Associated Diseases Als, Cancer, Colorectal Cancer, Tumor
KG Connections 25 edges

Introduction

flowchart TD
    PDK3["PDK3"] -->|"activates"| Colorectal_Cancer["Colorectal Cancer"]
    PDK3["PDK3"] -->|"activates"| Cancer["Cancer"]
    PDK3["PDK3"] -->|"activates"| Tumor["Tumor"]
    PDK3["PDK3"] -->|"activates"| Als["Als"]
    PDK3["PDK3"] -->|"activates"| HK2["HK2"]
    PDK3["PDK3"] -->|"activates"| PDK1["PDK1"]
    PDK3["PDK3"] -->|"activates"| MYC["MYC"]
    PDK3["PDK3"] -->|"activates"| Mitosis["Mitosis"]
    PDK3["PDK3"] -->|"activates"| GENES["GENES"]
    PDK3["PDK3"] -->|"activates"| Glycolysis["Glycolysis"]
    E2F1["E2F1"] -->|"activates"| PDK3["PDK3"]
    ENO1["ENO1"] -->|"activates"| PDK3["PDK3"]
    MYC["MYC"] -->|"activates"| PDK3["PDK3"]
    RB1["RB1"] -->|"associated with"| PDK3["PDK3"]
    style PDK3 fill:#4fc3f7,stroke:#333,color:#000

The PDK3 gene (3-Phosphoinositide-Dependent Protein Kinase 3) encodes a member of the phosphoinositide-dependent protein kinase (PDK) family. PDK3 is a serine/threonine kinase that plays important roles in cell survival, metabolism, and stress responses

. It is expressed in various tissues, with high expression in brain, and is implicated in neurodegenerative diseases and cancer.

Gene Information

Protein Structure

PDK3 contains characteristic features:

  • Kinase Domain: Serine/threonine kinase activity

  • PH Domain: Phosphoinositide binding (present in some isoforms)

  • Regulatory Regions: Autoinhibitory and activation segments

Normal Cellular Function

Cell Survival Signaling

  • Akt Activation: PDK3 phosphorylates and activates Akt/PKB

  • PKC Activation: Regulates protein kinase C isoforms

  • Cell Survival: Promotes cell survival under stress conditions

Metabolic Regulation

  • Glucose Metabolism: Insulin signaling pathway component

  • Lipid Metabolism: Affects lipid synthesis and storage

  • Mitochondrial Function: Regulates mitochondrial activity

Stress Responses

  • Oxidative Stress: Activated in response to ROS

  • DNA Damage: Involved in DNA damage responses

  • Hypoxia: Regulates hypoxic responses

Expression Pattern

PDK3 is widely expressed:

  • Brain: Neurons in cortex, hippocampus, cerebellum

  • Heart, skeletal muscle

  • Liver, kidney

  • Pancreas

Expression is regulated by developmental stage and metabolic conditions.

Disease Associations

Alzheimer’s Disease

  • Tau Phosphorylation: May contribute to tau pathology

  • Cell Survival: Dysregulation affects neuronal viability

  • Metabolic Dysfunction: Links to brain metabolic deficits

Parkinson’s Disease

  • Dopaminergic Neurons: Altered expression in substantia nigra

  • Mitochondrial Function: Regulates mitochondrial health

Cancer

  • Oncogenic Role: Overexpressed in various cancers

  • Cell Proliferation: Promotes cancer cell growth

  • Therapeutic Target: PDK3 inhibitors in development

Metabolic Disorders

  • Diabetes: Altered insulin signaling

  • Obesity: Metabolic dysfunction

Signaling Pathways

PDK3 participates in multiple pathways:

  • PI3K/Akt Pathway: Central cell survival pathway

  • mTOR Pathway: Growth and metabolism regulation

  • AMPK Pathway: Energy sensing

  • MAPK Pathway: Stress responses

Therapeutic Targeting

Research Highlights

  • PDK3 knockout mice show developmental abnormalities

  • PDK3 promotes neuronal survival under stress conditions

  • Targeting PDK3 shows therapeutic potential in models

See Also

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