Erbb4 Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
ERBB4 (Erb-B2 Receptor Tyrosine Kinase 4) encodes a member of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases. Also known as HER4, ERBB4 plays crucial roles in development, particularly in the nervous system, heart, and mammary gland. The gene is located on chromosome 2q34 and has been implicated in various neurological disorders.
| Attribute |
Value |
| Gene Symbol |
ERBB4 |
| Official Full Name |
Erb-B2 Receptor Tyrosine Kinase 4 |
| Synonyms |
HER4, TYRO1 |
| Chromosomal Location |
2q34 |
| HGNC ID |
HGNC:3432 |
| Entrez Gene ID |
2066 |
| UniProt ID |
Q15303 |
¶ Protein Structure and Function
ERBB4 is a transmembrane receptor tyrosine kinase with an extracellular ligand-binding domain, a transmembrane helix, and an intracellular tyrosine kinase domain. Upon ligand binding (including neuregulins, heregulins, and betacellulin), ERBB4 forms homodimers or heterodimers and activates multiple signaling pathways.
- PI3K/AKT pathway: Cell survival, metabolism, and growth
- MAPK/ERK pathway: Cell proliferation and differentiation
- STAT pathway: Gene transcription and cellular responses
- PLCγ pathway: Calcium signaling and cytoskeletal reorganization
- Receptor tyrosine kinase signaling
- Neural development and myelination
- Synaptic plasticity
- Astrocyte function
- Cardiac development
ERBB4 is expressed in:
- Brain (cortex, hippocampus, cerebellum)
- Heart
- Mammary gland
- Skeletal muscle
- Various peripheral tissues
In the brain, ERBB4 is expressed in neurons and astrocytes, particularly in regions involved in learning and memory.
- ERBB4 is involved in Aβ (amyloid-beta) toxicity
- Neuregulin-ERBB4 signaling is impaired in AD
- ERBB4 regulates GABAergic interneuron function
- May affect amyloid processing and synaptic plasticity
- ERBB4 variants associated with PD risk
- Involved in dopaminergic neuron survival
- Neuregulin-ERBB4 signaling protects against MPTP toxicity
- ERBB4 is a susceptibility gene for schizophrenia
- Dysregulated ERBB4 signaling affects synaptic function
- Alters GABAergic and glutamatergic neurotransmission
- ERBB4 expression altered in epileptic tissue
- May contribute to hyperexcitability
- ERBB4 is overexpressed in some cancers
- Can function as a tumor suppressor or oncogene depending on context
- Soluble ERBB4 isoforms have anti-tumor effects
- ERBB4 agonists: Neuregulin-1 for demyelinating disorders
- ERBB4 modulators: For AD and PD neuroprotection
- HER4-targeted antibodies: For cancer therapy
- CNS penetration is a challenge for systemically delivered drugs
- Isoform-specific targeting may provide better outcomes
- Combination approaches targeting multiple ERBB family members
- Erbb4 knockout mice: Embryonic lethal (cardiac defects)
- Conditional knockout models: Reveal role in neural development
- Transgenic models: Overexpression studies in neurodegeneration
The study of Erbb4 Gene 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.
- PMID:14504290 - ERBB4 and neuregulin signaling in the brain
- PMID:15994097 - ERBB4 in Alzheimer's disease
- PMID:18687677 - ERBB4 variants and Parkinson's disease
- PMID:20660478 - ERBB4 in schizophrenia
- PMID:22573322 - ERBB4 therapeutic targeting
- PMID:24142144 - Neuregulin-ERBB4 in neuroprotection
- PMID:25669886 - ERBB4 isoforms in cancer
- PMID:29452125 - ERBB4 and GABAergic signaling