.infobox .infobox-protein
!!! Info
- Protein Name: Fibroblast Growth Factor Receptor 1 (FGFR1)
- Gene: FGFR1
- UniProt: P11362
- PDB: 1evs, 2cr7, 5w5j
- Molecular Weight: 92.0 kDa (FGFR1c isoform)
- Subcellular Localization: Cell surface, Endosomes (after ligand binding)
- Protein Family: FGFR family, Receptor tyrosine kinase
Fibroblast Growth Factor Receptor 1 (FGFR1) is a receptor tyrosine kinase that plays critical roles in neuronal development, survival, and plasticity. As part of the FGFR family, FGFR1 binds fibroblast growth factors (FGFs) to activate downstream signaling pathways including RAS/MAPK, PI3K/AKT, and PLCG [1]. In the central nervous system, FGFR1 is essential for neurogenesis, neural stem cell maintenance, and synaptic plasticity [1]. Dysregulation of FGFR1 signaling has been implicated in Alzheimer's disease, Parkinson's disease, and various neuropsychiatric disorders [2][3]. [1]
FGFR1 is a single-pass transmembrane receptor composed of an extracellular ligand-binding domain with three immunoglobulin-like domains (IgI-IgIII), a transmembrane helix, and an intracellular tyrosine kinase domain [1]. The receptor exists in multiple splice isoforms (FGFR1b, FGFR1c) with distinct ligand affinities. Upon FGF binding to the extracellular domain, FGFR1 dimerizes and undergoes autophosphorylation, activating its intracellular tyrosine kinase activity. Structural studies have revealed the molecular basis for FGF-FGFR interactions, with the Ig2 and Ig3 domains mediating ligand binding specificity. [2]
FGFR1 signaling is activated by multiple FGF ligands including FGF1 (acidic FGF), FGF2 (basic FGF), FGF4, and others [1]. In the nervous system: [3]
FGFR1 signaling is implicated in Alzheimer's disease through multiple mechanisms: [4]
In PD, FGFR1 plays complex roles: [5]
Several therapeutic strategies targeting FGFR1 are under development: [6]
Fibroblast growth factor receptor-1 regulates dopamine transmission (2020). 2020. ↩︎
FGF2/FGFR1 signaling promotes neural stem cell maintenance (2021). 2021. ↩︎
FGFR1 and synaptic plasticity in Alzheimer's disease (2018). 2018. ↩︎
Therapeutic potential of FGF analogs in neurodegenerative disease (2021). 2021. ↩︎
FGFR1 in depression and antidepressant response (2019). 2019. ↩︎
Blood-brain barrier permeability and neurotrophic factor delivery (2020). 2020. ↩︎