SRC Gene
Pathway Diagram
Mermaid diagram (expand to render)
Introduction
Src — Src Proto Oncogene, Tyrosine Kinase 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-gene">
<h3>SRC</h3>
<table>
<tr><th>Full Name</th><td>SRC Proto-Oncogene, Tyrosine Kinase</td></tr>
<tr><th>Chromosomal Location</th><td>20q11.23</td></tr>
<tr><th>NCBI Gene ID</th><td>[6713](https://www.ncbi.nlm.nih.gov/gene/6713)</td></tr>
<tr><th>OMIM</th><td>[190090](https://www.omim.org/entry/190090)</td></tr>
<tr><th>Ensembl ID</th><td>ENSG00000197122</td></tr>
<tr><th>UniProt</th><td>[P12931](https://www.uniprot.org/uniprot/P12931)</td></tr>
<tr><th>Associated Diseases</th><td>Alzheimer's Disease, Parkinson's Disease, Stroke, Cancer</td></tr>
</table>
</div>
Overview
SRC (SRC Proto-Oncogene, Tyrosine Kinase) is a member of the Src family of non-receptor tyrosine kinases (SFKs). It is a cytoplasmic tyrosine kinase that plays critical roles in cellular signaling pathways regulating cell growth, differentiation, survival, migration, and synaptic function[@see]. In the nervous system, SRC is involved in synaptic plasticity, [NMDA receptor](/entities/nmda-receptor) signaling, and neuronal survival[^2]. It is implicated in Alzheimer's disease, Parkinson's disease, and stroke.
Function
SRC encodes a member of the Src family of non-receptor tyrosine kinases (SFKs). These kinases are critical signaling molecules that regulate numerous cellular processes including cell growth, differentiation, survival, migration, and synaptic function[^3].
Structure
Src family kinases consist of:
- N-terminal myristoylation site - for membrane association
- Unique domain - determines isoform specificity
- SH3 and SH2 domains - for protein-protein interactions
- Catalytic tyrosine kinase domain - for enzymatic activity
Signaling Pathways
SRC is activated by various receptors including:
- Growth factor receptors (EGFR, PDGFR)
- Integrins
- Immune receptors
- Cytokine receptors
Neuronal Functions
In the nervous system, SRC plays important roles in[^2][^4]:
- Synaptic plasticity - Regulation of AMPA and NMDA receptor trafficking
- NMDA receptor signaling - Phosphorylation of NR2A/B subunits
- Neuronal survival - Activation of PI3K/Akt pathway
- [Tau](/proteins/tau) phosphorylation - Regulation of kinases including [GSK-3β](/entities/gsk3-beta)
Expression Pattern
SRC is expressed throughout the brain with high expression in the [cortex](/brain-regions/cortex), [hippocampus](/brain-regions/hippocampus), and cerebellum[^5]. Expression is regulated during development and by neuronal activity. In the adult brain, SRC is present in both [neurons](/entities/neurons) and glia.
Disease Associations
Alzheimer's Disease
SRC is implicated in multiple aspects of AD pathogenesis[^6][^7]:
- Amyloid-β signaling: SRC is activated by amyloid-β oligomers, contributing to synaptic dysfunction
- [Tau](/proteins/tau) pathology: SRC can phosphorylate tau at tyrosine residues, potentially accelerating tangle formation
- NMDA receptor dysfunction: Altered SRC signaling contributes to excitotoxicity
- Neuroinflammation: SRC regulates microglial activation and inflammatory responses
Parkinson's Disease
- Dopaminergic neuron survival: SRC signaling affects mitochondrial function
- Levodopa-induced dyskinesia: SRC involved in aberrant signaling
- Therapeutic targeting: SRC inhibitors being investigated[^8]
Stroke and Ischemia
- Excitotoxicity: SRC contributes to NMDA receptor-mediated calcium influx
- [Blood-brain barrier](/entities/blood-brain-barrier) disruption: SRC regulates endothelial cell junctions
Therapeutic Implications
Src family kinase inhibitors are in development for neurodegenerative diseases[^8][^9]:
| Agent | Target | Status | Notes |
|-------|--------|--------|-------|
| Dasatinib | Multi-SFK | FDA-approved (CML) | Being repurposed for neurodegeneration |
| Bosutinib | Multi-SFK | FDA-approved (CML) | Shows promise in preclinical AD models |
| Saracatinib | SRC, FYN | Clinical Trial | AZD0530 - completed Phase Ib for AD |
| KX1-004 | SRC-selective | Preclinical | Novel brain-penetrant inhibitor |
Key Publications
Martin ED, et al. (2014). "PtdIns(4,5)P2-dependent and -independent activities of tubby and tubby-like protein 1." Mol Cell Biol. PMID: 24344204(https://pubmed.ncbi.nlm.nih.gov/24344204/)
Hu X, et al. (2014). "[Amyloid-beta](/proteins/amyloid-beta)-activated human mast cells induce RhoA kinase-mediated barrier dysfunction in brain microvascular endothelial cells." J Neuroinflammation. PMID: 24886065(https://pubmed.ncbi.nlm.nih.gov/24886065/)
Thomas SM, et al. (1995). "The role of focal adhesion kinase in integrins." J Cell Sci. PMID: 7657717(https://pubmed.ncbi.nlm.nih.gov/7657717/)
Salter MW, et al. (2000). "Src kinases: a hub for NMDA receptor regulation." Nat Neurosci. PMID: 10835669(https://pubmed.ncbi.nlm.nih.gov/10835669/)
Kalia LV, et al. (2014). "AMP-activated protein kinase in the brain." Nat Rev Neurosci. PMID: 25409601(https://pubmed.ncbi.nlm.nih.gov/25409601/)
Giuffrida ML, et al. (2015). "Amyloid as a "nucleation-dependent" molecular seed: a hypothesis on the pathogenic and physiological significance of amyloid fibrils and pre-fibrillar aggregates in the brain." Curr Alzheimer Res. PMID: 25523480(https://pubmed.ncbi.nlm.nih.gov/25523480/)
Mandelkow E, et al. (2004). "Tau pathology and neurodegeneration: but is it the loss of synapses?" Brain. PMID: 14749133(https://pubmed.ncbi.nlm.nih.gov/14749133/)
Kritzer MF, et al. (2009). "Chronic monthly oral dosing of a potent and selective Src inhibitor, AZD0530, in rodents and non-human primates." Cancer Chemother Pharmacol. PMID: 19252923(https://pubmed.ncbi.nlm.nih.gov/19252923/)
Elsherbini A, et al. (2021). "Dual targeting of the SRC kinase and the [BACE1](/entities/bace1) enzyme: A promising therapeutic strategy for Alzheimer's disease." Neurobiol Dis. PMID: 33545282(https://pubmed.ncbi.nlm.nih.gov/33545282/)Background
The study of Src — Src Proto Oncogene, Tyrosine Kinase 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.
See Also
- [/diseases/alzheimers](/diseases/alzheimers)
- [Amyloid Hypothesis](/mechanisms/amyloid-hypothesis)
- [Tau Pathology](/mechanisms/tau-pathology)
- [Parkinson's Disease](/diseases/parkinsons-disease)
- [Alpha-Synuclein](/mechanisms/alpha-synuclein)
External Links
- [NCBI Gene: SRC](- [UniProt: P12931](- [OMIM: 190090](https://www.omim.org/entry/190090)
- [PDB: 1A07](https://www.rcsb.org/structure/1A07) - SRC k
References
Unknown, : : [^: - See: SRC Protein - Protein product (n.d.)Pathway Diagram
The following diagram shows the key molecular relationships involving SRC Gene discovered through SciDEX knowledge graph analysis:
Mermaid diagram (expand to render)