GRB2 — Growth Factor Receptor Bound Protein 2

GRB2 — Growth Factor Receptor Bound Protein 2

Pathway Diagram

```mermaid
flowchart TD
GRB2["GRB2<br/>Growth Factor Receptor<br/>Bound Protein 2"]

LRRK2["LRRK2<br/>Leucine Rich Repeat<br/>Kinase 2"]
STING1["STING1<br/>Stimulator of<br/>Interferon Genes"]
STAT3["STAT3<br/>Signal Transducer<br/>Activator 3"]
IFNG["IFNG<br/>Interferon Gamma"]

ATG16L1["ATG16L1<br/>Autophagy Related<br/>16 Like 1"]
BECN1["BECN1<br/>Beclin 1<br/>Autophagy Regulator"]
LC3["LC3<br/>Microtubule Associated<br/>Protein 1LC3"]
GABARAP["GABARAP<br/>GABA Receptor<br/>Associated Protein"]
RB1CC1["RB1CC1<br/>RB1 Inducible<br/>Coiled Coil 1"]

MAPK14["MAPK14<br/>p38 MAPK"]
RIPK1["RIPK1<br/>Receptor Interacting<br/>Kinase 1"]
ERN1["ERN1<br/>Endoplasmic Reticulum<br/>Nuclei 1"]
EIF2AK3["EIF2AK3<br/>PERK Kinase"]

ALS["ALS<br/>Amyotrophic Lateral<br/>Sclerosis"]
MS["Multiple Sclerosis<br/>Neuroinflammation"]
INFLAMMATION["Chronic<br/>Neuroinflammation"]
FIBROSIS["Tissue<br/>Fibrosis"]

GRB2 -->|"interacts with"| LRRK2
GRB2 -->|"activates"| STING1
GRB2 -->|"regulates"| STAT3
STING1 -->|"induces"| IFNG
STAT3 -->|"promotes"| INFLAMMATION

GRB2 -->|"modulates"| ATG16L1
GRB2 -->|"interacts with"| BECN1
GRB2 -->|"regulates"| LC3
ATG16L1 -->|"promotes"| LC3
BECN1 -->|"initiates"| LC3
LC3 -->|"controls"| GABARAP

GRB2 -->|"activates"| MAPK14
GRB2 -->|"modulates"| RIPK1
MAPK14 -->|"promotes"| INFLAMMATION
RIPK1 -->|"triggers"| INFLAMMATION

GRB2

GRB2 — Growth Factor Receptor Bound Protein 2

Pathway Diagram

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">GRB2 — Growth Factor Receptor Bound Protein 2</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td><strong>GRB2</strong></td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Growth Factor Receptor Bound Protein 2</td>
</tr>
<tr>
<td class="label">Chromosome</td>
<td>17q25.1</td>
</tr>
<tr>
<td class="label">NCBI Gene</td>
<td><a href="https://www.ncbi.nlm.nih.gov/gene/2885" target="_blank">2885</a></td>
</tr>
<tr>
<td class="label">Ensembl</td>
<td><a href="https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000177885" target="_blank">ENSG00000177885</a></td>
</tr>
<tr>
<td class="label">OMIM</td>
<td><a href="https://www.omim.org/entry/108355" target="_blank">108355</a></td>
</tr>
<tr>
<td class="label">UniProt</td>
<td><a href="https://www.uniprot.org/uniprot/P62993" target="_blank">P62993</a></td>
</tr>
<tr>
<td class="label">Diseases</td>
<td>[AD](/diseases/alzheimers), [PD](/diseases/parkinsons-disease), [ALS](/diseases/als), cancer (driver)</td>
</tr>
<tr>
<td class="label">Expression</td>
<td>Ubiquitous ([neurons](/entities/neurons), glia, all tissues)</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">ALS</a>, <a href="/wiki/aging" style="color:#ef9a9a">Aging</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">Alzheimer</a>, <a href="/wiki/amyotrophic-lateral-sclerosis" style="color:#ef9a9a">Amyotrophic Lateral Sclerosis</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">247 edges</a></td>
</tr>
</table>

GRB2 (Growth Factor Receptor Bound Protein 2)

Introduction

GRB2 (Growth Factor Receptor Bound Protein 2) is a critical adaptor protein that links receptor tyrosine kinases to downstream signaling pathways[@schlessinger2000][@margolis1992]. This page provides detailed information about its structure, function, and role in neurodegeneration.

Overview

GRB2 is an adaptor protein encoded by the GRB2 gene on chromosome 17q25.1. It contains one SH2 domain flanked by two SH3 domains, allowing it to link activated receptor tyrosine kinases (RTKs) to the RAS/MAPK and PI3K/AKT signaling cascades[^3]. GRB2 is essential for cellular proliferation, differentiation, survival, and synaptic plasticity.

Function

Signal Transduction

GRB2 serves as a molecular adaptor:

Synaptic Plasticity

GRB2 is involved in:

• [NMDA receptor](/entities/nmda-receptor) signaling
• AMPA receptor trafficking
• Dendritic spine formation
• [Long-term potentiation](/mechanisms/long-term-potentiation) (LTP)

Neurotrophin Signaling

GRB2 binds to activated Trk receptors (TrkA, TrkB, TrkC) linking NGF, BDNF, and NT-3 signaling to neuronal survival pathways.

Disease Associations

Alzheimer's Disease

• GRB2 interacts with APP and regulates [amyloid precursor protein](/entities/app-protein) processing
• Altered GRB2 expression in AD brain
• Role in [tau](/proteins/tau) phosphorylation via RAS/RAF/ERK pathway
• GRB2 polymorphisms associated with AD risk

Parkinson's Disease

• GRB2 involved in dopaminergic neuron survival
• Links LRRK2 signaling to downstream pathways
• Altered in PD models

ALS

• GRB2 in motor neuron survival signaling
• Links to neurotrophin receptors
• Altered in ALS models

Cancer

GRB2 is frequently amplified or overexpressed in cancers:

• Breast cancer
• Lung cancer
• Colon cancer
• Driver mutation in some tumors

Expression Pattern

GRB2 is ubiquitously expressed:

• Neurons ([cortex](/brain-regions/cortex), [hippocampus](/brain-regions/hippocampus), basal ganglia)
• Glial cells ([astrocytes](/entities/astrocytes), microglia)
• All peripheral tissues
• High expression in developing brain

Therapeutic Implications

Drug Targets

• GRB2-SH2 domain inhibitors in development
• Targeting RTK-GRB2 interaction for cancer therapy

Neurological Applications

• Modulating GRB2 signaling for neuroprotection
• BDNF/TrkB-GRB2 pathway in AD/PD therapy

Key Publications

Cross-References

• [RAS/MAPK signaling pathway](/mechanisms/ras-mapk-pathway)
• [PI3K/AKT signaling pathway](/mechanisms/pi3k-akt-pathway)
• [Trk receptors](/genes/ntrk1)
• [BDNF gene](/genes/bdnf)
• [EGFR gene](/genes/egfr)
• [Alzheimer's disease signaling](/diseases/alzheimers-disease)
• [Parkinson's disease mechanisms](/diseases/parkinsons-disease)

See Also

• [RAS/MAPK signaling pathway](/mechanisms/ras-mapk-pathway)
• [PI3K/AKT signaling pathway](/mechanisms/pi3k-akt-pathway)
• [Alzheimer's disease signaling](/diseases/alzheimers-disease)
• [Parkinson's disease mechanisms](/diseases/parkinsons-disease)

External Links

• [Ensembl: ENSG00000177885](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000177885)

References

Pathway Diagram

The following diagram shows the key molecular relationships involving GRB2 — Growth Factor Receptor Bound Protein 2 discovered through SciDEX knowledge graph analysis: