Fibroblast growth factor receptor substrate 2 phosphotyrosine-binding domain (FRS2 PTB domain) (FRS2 PTB domain)

Fibroblast growth factor receptor substrate 2 (FRS2) is a key adaptor protein that facilitates signaling from fibroblast growth factor receptors (FGFRs) and other receptor tyrosine kinases (UniProt Q9GZV9). The phosphotyrosine-binding (PTB) domain of FRS2 is responsible for its specific recruitment to the juxtamembrane region of activated FGFRs (PMID: 15121841). Upon binding, FRS2 undergoes extensive tyrosine phosphorylation, providing docking sites for downstream signaling molecules like Grb2 and Shp2 (PMID: 18400050). This process is vital for the activation of the Ras/MAPK and PI3K/Akt pathways, which regulate cell growth, survival, and differentiation. In several cancers, such as liposarcoma and breast cancer, FRS2 is frequently overexpressed or its gene is amplified, leading to hyperactivation of these pathways (PMID: 25664583). Targeting the FRS2 PTB domain with small molecules or peptidomimetics aims to disrupt the FGFR-FRS2 interaction, offering a potential therapeutic strategy to inhibit oncogenic signaling (PMID: 22493231).

Other names

FRS2aFRS2alphaSNT1SNT-1FGFR-signaling adaptor SNT1

Inhibition of protein-protein interaction (PPI) between the FRS2 PTB domain and the FGFR juxtamembrane region (PMID: 22493231).