YES1 (YES Proto-Oncogene 1, Src Family Tyrosine Kinase) is a member of the Src family of non-receptor tyrosine kinases (SFKs). It is widely expressed in various tissues including the brain, where it participates in signaling pathways controlling cell proliferation, differentiation, and survival. YES1 is involved in neural development, synaptic function, and has emerging roles in neurodegenerative disease pathogenesis [1].
| YES1 Gene | |
|---|---|
| Official Symbol | YES1 |
| Full Name | YES Proto-Oncogene 1, Src Family Tyrosine Kinase |
| Chromosomal Location | 18p11.32 |
| NCBI Gene ID | https://www.ncbi.nlm.nih.gov/gene/7524 7524 |
| OMIM | https://www.omim.org/entry/164880 164880 |
| Ensembl ID | ENSG00000106105 |
| UniProt ID | https://www.uniprot.org/uniprot/P42681 P42681 |
| Associated Diseases | AD, PD, cancer, stroke |
YES1 encodes a 536-amino acid protein member of the Src family of non-receptor tyrosine kinases (SFKs). The protein structure includes:
The protein undergoes conformational regulation through intramolecular interactions between the SH3 domain and a polyproline region, and between the SH2 domain and a C-terminal regulatory tyrosine (Y527 in Src, Y536 in YES1).
YES1 plays important roles in multiple neuronal processes:
Synaptic Plasticity: YES1 is enriched in synaptic fractions and regulates AMPA and NMDA receptor trafficking [4]. It phosphorylates PSD-95 and other scaffolding proteins at synapses, modulating synaptic strength and plasticity.
NMDA Receptor Signaling: YES1 phosphorylates NMDA receptor subunits (GluN2A/B), influencing receptor trafficking and downstream signaling pathways involved in synaptic plasticity and memory formation.
Tau Phosphorylation: YES1 can phosphorylate tau protein at multiple sites, including Y197, contributing to tau pathology in Alzheimer's disease [2].
Amyloid-β Processing: YES1 regulates amyloid precursor protein (APP) processing and Aβ production through modulation of α- and β-secretase activity [1].
Neuroinflammation: YES1 signaling in microglia modulates inflammatory responses and cytokine production in Parkinson's disease models [3].
YES1 participates in multiple signaling cascades:
YES1 contributes to AD pathogenesis through multiple mechanisms:
YES1 is expressed throughout the brain:
Several strategies targeting YES1 are under investigation:
| Agent | Type | Status | Notes |
|---|---|---|---|
| Dasatinib | Multi-kinase inhibitor | Preclinical | FDA-approved for CML, being repurposed |
| Bosutinib | SFK inhibitor | Preclinical | Shows neuroprotection |
| YES1-selective | Under development | Discovery | Higher specificity |