Tyrosine-protein kinase Yes (YES1) (YES1)

Tyrosine-protein kinase Yes (YES1) is a non-receptor protein tyrosine kinase that serves as a key mediator in intracellular signal transduction pathways. As a member of the Src family kinases (SFKs), it is the cellular homolog of the Yamaguchi sarcoma virus oncogene and is integral to the regulation of cell growth, survival, and migration (UniProt P07947). YES1 is frequently found to be overexpressed or amplified in various malignancies, including lung, esophageal, and head and neck cancers, where it promotes epithelial-to-mesenchymal transition and metastasis (PubMed: 30120244). Beyond its role as a primary oncogenic driver, YES1 has been identified as a significant mechanism of acquired resistance to other targeted therapies, such as EGFR inhibitors in non-small cell lung cancer (PubMed: 25164407). Therapeutically, YES1 is targeted by multi-kinase inhibitors like dasatinib, though these drugs often hit multiple members of the Src family. Current drug development efforts focus on identifying more selective YES1 inhibitors to minimize systemic toxicity and overcome resistance in specific patient populations (PubMed: 32444465).

Other names

c-Yesp61-YesProto-oncogene c-YesYESYamaguchi sarcoma viral oncogene homolog 1

Inhibition of the kinase domain through ATP-competitive binding, preventing the phosphorylation of downstream signaling substrates.