Insulin-Like Growth Factor 1 Receptor Protein

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Insulin-Like Growth Factor 1 Receptor Protein

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Insulin-Like Growth Factor 1 Receptor Protein

Introduction

Insulin Like Growth Factor 1 Receptor 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.

<div class="infobox infobox-protein"> [@girnita2007]
<div class="infobox-header">Insulin-Like Growth Factor 1 Receptor (IGF1R)</div> [@russo2009]
<div class="infobox-content"> [@cheng2013]
<table> [@bassil2014]
<tr><th>Protein Name</th><td>Insulin-Like Growth Factor 1 Receptor</td></tr> [@cohen2009]
<tr><th>Gene</th><td>[IGF1R](/genes/igf1r)</td></tr> [@llorensmartin2013]
<tr><th>UniProt ID</th><td>[P08069](https://www.uniprot.org/uniprotkb/P08069/entry)</td></tr> [@torresaleman2012]
<tr><th>Molecular Weight</th><td>180 kDa (alpha + beta chains)</td></tr>
<tr><th>Subcellular Localization</th><td>Cell Membrane</td></tr>
<tr><th>Protein Family</th><td>Insulin receptor family, Receptor tyrosine kinases</td></tr>
<tr><th>Associated Diseases</th><td>Alzheimer's Disease, Parkinson's Disease, ALS, Cancer, Laron Syndrome</td></tr>
</table>
</div>
</div>

Overview

The Insulin-Like Growth Factor 1 Receptor (IGF1R) is a transmembrane receptor tyrosine kinase that mediates the cellular effects of IGF1. This receptor is widely expressed in the brain and plays essential roles in neuronal development, synaptic plasticity, and neuroprotection. IGF1R is a critical therapeutic target for neurodegenerative diseases due to its potent neurotrophic effects.

Structure

...

Insulin-Like Growth Factor 1 Receptor Protein

Introduction

Insulin Like Growth Factor 1 Receptor 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.

<div class="infobox infobox-protein"> [@girnita2007]
<div class="infobox-header">Insulin-Like Growth Factor 1 Receptor (IGF1R)</div> [@russo2009]
<div class="infobox-content"> [@cheng2013]
<table> [@bassil2014]
<tr><th>Protein Name</th><td>Insulin-Like Growth Factor 1 Receptor</td></tr> [@cohen2009]
<tr><th>Gene</th><td>[IGF1R](/genes/igf1r)</td></tr> [@llorensmartin2013]
<tr><th>UniProt ID</th><td>[P08069](https://www.uniprot.org/uniprotkb/P08069/entry)</td></tr> [@torresaleman2012]
<tr><th>Molecular Weight</th><td>180 kDa (alpha + beta chains)</td></tr>
<tr><th>Subcellular Localization</th><td>Cell Membrane</td></tr>
<tr><th>Protein Family</th><td>Insulin receptor family, Receptor tyrosine kinases</td></tr>
<tr><th>Associated Diseases</th><td>Alzheimer's Disease, Parkinson's Disease, ALS, Cancer, Laron Syndrome</td></tr>
</table>
</div>
</div>

Overview

The Insulin-Like Growth Factor 1 Receptor (IGF1R) is a transmembrane receptor tyrosine kinase that mediates the cellular effects of IGF1. This receptor is widely expressed in the brain and plays essential roles in neuronal development, synaptic plasticity, and neuroprotection. IGF1R is a critical therapeutic target for neurodegenerative diseases due to its potent neurotrophic effects.

Structure

IGF1R is a heterotetrameric receptor composed of two α-β subunits:

Extracellular α-Chains (706 aa each)

Ligand-binding domain: Contains multiple repeats of leucine-rich motifs
Cysteine-rich regions: Provide structural stability
Fibronectin type III domains: Facilitate receptor dimerization

Transmembrane β-Chains (626 aa each)

Single transmembrane helix: Anchors receptor in membrane
Tyrosine kinase domain: Catalytic core (residues 1085-1281)
C-terminal tail: Contains regulatory tyrosine residues

Key Structural Features

Receptor Dimerization: Ligand binding induces receptor dimerization

Autophosphorylation Sites: Tyr 1131, 1135, 1136 (kinase activation)

Substrate Docking Sites: Tyr 950 ([IRS-1](/entities/irs1) binding)

Cleavage Site: α-β subunit cleavage at furin convertase site

Normal Function

Neurotrophic Signaling

IGF1R mediates essential neuronal functions:

Neuronal Survival: Activates PI3K/Akt pathway preventing [apoptosis](/entities/apoptosis)

Synaptic Plasticity: Regulates [NMDA](/entities/nmda-receptor) receptor function and [LTP](/mechanisms/long-term-potentiation)

Neurogenesis: Promotes neural progenitor cell proliferation

Dendritic Growth: Stimulates dendritic arborization

Myelination: Supports oligodendrocyte maturation

Metabolic Support: Enhances glucose uptake and mitochondrial function

Signaling Pathways

Primary Pathways

PI3K/Akt Cascade:

IRS-1/2 recruitment to phosphorylated Tyr 950
PI3K activation → PIP3 generation
Akt phosphorylation and activation
Downstream effects on survival, growth, and metabolism

MAPK/ERK Cascade:

Shc/Grb2/Sos complex formation
Ras-Raf-MEK-ERK activation
Nuclear transcription activation

Secondary Effects

mTORC1 activation (protein synthesis)
[GSK-3β](/entities/gsk3-beta) inhibition ([tau](/proteins/tau) phosphorylation regulation)
CREB activation (gene transcription)
[NF-κB](/entities/nf-kb) regulation (inflammation)

Role in Neurodegeneration

Alzheimer's Disease

IGF1R involvement in AD is complex:

Expression Changes: Altered receptor expression in AD brain regions
[Aβ](/proteins/amyloid-beta) Interaction: Amyloid-β oligomers disrupt IGF1R signaling
Insulin Resistance: Shared signaling defects with insulin signaling
Therapeutic Target: Agonists may restore neuroprotective signaling

Parkinson's Disease

IGF1R provides neuroprotection:

Dopaminergic Neuron Survival: Receptor protects SNpc [neurons](/entities/neurons)
Mitochondrial Function: Enhances mitochondrial biogenesis
[α-Synuclein](/proteins/alpha-synuclein) Clearance: May facilitate protein clearance pathways
Clinical Studies: IGF1R agonists under investigation

ALS

IGF1R signaling is impaired:

Motor Neuron Vulnerability: Reduced receptor expression in ALS
Therapeutic Potential: Gene therapy approaches delivering IGF1
Combination Therapy: With other neurotrophic factors

Cancer

IGF1R is overexpressed in many cancers:

Proliferation Signal: Drives cancer cell growth
Therapeutic Target: Antibodies and TKIs in development
Resistance Mechanisms: Cancer cells develop IGF1R dependency

Therapeutic Targeting

Agonists

Recombinant IGF1: Ibutamoren (oral GH secretagogue)
IGF1 Analogs: Modified peptides with enhanced activity
Monoclonal Antibodies: Agonistic antibodies in development

Antagonists

Blocking Antibodies: Prevent ligand binding
Tyrosine Kinase Inhibitors: Small molecule inhibitors
IGF1R-specific: Selective vs. IR cross-reactivity

Gene Therapy

AAV-mediated IGF1R activation
Neuron-specific expression cassettes
Combination with neurotrophic factors

Biomarkers

IGF1R as a biomarker:

Receptor Density: Measured via PET ligands
Phosphorylation Status: p-IGF1R indicates active signaling
Expression Levels: Altered in disease states
Therapeutic Response: Biomarker for treatment efficacy

Animal Models

Knockout Studies

IGF1R null: Embryonic lethal (growth deficiency)
Neuron-specific knockout: Neuronal loss, behavioral deficits

Transgenic Models

IGF1R overexpression: Enhanced neuroprotection
Dominant negative: Accelerated neurodegeneration

Background

The study of Insulin Like Growth Factor 1 Receptor 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.

External Links

[UniProt: IGF1R](https://www.uniprot.org/uniprotkb/P08069/entry)
[NCBI Protein: IGF1R](https://www.ncbi.nlm.nih.gov/protein)
[PDB: IGF1R Structure](https://www.rcsb.org/structure/1IGR)
[Human IGF1R Gene](https://www.genecards.org/cgi-bin/carddisp.pl?gene=IGF1R)

References

[De Meyts P, et al, (1994) (1994)](https://pubmed.ncbi.nlm.nih.gov/7837361/)

[Girnita L, et al, (2007) (2007)](https://pubmed.ncbi.nlm.nih.gov/17728824/)

[Russo VC, et al, (2009) (2009)](https://pubmed.ncbi.nlm.nih.gov/19544455/)

[Cheng CM, et al, (2013) (2013)](https://pubmed.ncbi.nlm.nih.gov/23474339/)

[Bassil F, et al, (2014) (2014)](https://pubmed.ncbi.nlm.nih.gov/25142614/)

[Cohen E, et al, (2009) (2009)](https://pubmed.ncbi.nlm.nih.gov/19627270/)

[Llorens-Martin M, et al, (2013) (2013)](https://pubmed.ncbi.nlm.nih.gov/23657946/)

[Unknown, Torres-Aleman I (2012). IGF-1 and brain repair. Pharmacol Res. 65:545-549 (2012)](https://pubmed.ncbi.nlm.nih.gov/22330061/)

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Related Entities

IGF1RPROTEIN

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📊 Evidence Profile Foundational

Evidence Balance

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Certainty

100%

Debates

0

Incoming

20

Outgoing

26

0 supporting 0 contradicting 0 neutral

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📗 Cite This Artifact

Insulin-Like Growth Factor 1 Receptor Protein

Insulin-Like Growth Factor 1 Receptor Protein

Introduction

Overview

Structure

Insulin-Like Growth Factor 1 Receptor Protein

Introduction

Overview

Structure

Extracellular α-Chains (706 aa each)

Transmembrane β-Chains (626 aa each)

Key Structural Features

Normal Function

Neurotrophic Signaling

Signaling Pathways

Primary Pathways

Secondary Effects

Role in Neurodegeneration

Alzheimer's Disease

Parkinson's Disease

ALS

Cancer

Therapeutic Targeting

Agonists

Antagonists

Gene Therapy

Biomarkers

Animal Models

Knockout Studies

Transgenic Models

Background

See Also

External Links

References

💬 Discussion