Fibroblast growth factor receptor substrate 2 (FRS2)

Fibroblast growth factor receptor substrate 2 (FRS2) is a membrane-anchored signal transducing adaptor protein that mediates signal transduction from activated receptor tyrosine kinases (RTKs), most notably the fibroblast growth factor receptors (FGGRs), but also neurotrophin receptors, RET, ALK, and others. Upon activation of these receptors, FRS2 is phosphorylated on tyrosine residues, serving as a docking site for downstream effectors such as Grb2, Shp2, Gab1, and Cbl. It orchestrates activation of key signaling pathways, including the MAPK/ERK and PI3K/AKT cascades, thereby regulating cell proliferation, migration, survival, and differentiation. FRS2 is essential for embryonic development, and its gene amplification or overexpression is implicated in several cancers, where it can be a biomarker for FGFR signaling dependency. FRS2 is not currently a direct therapeutic target, but its phosphorylation status can be modulated by drugs acting on upstream RTKs, particularly FGFR inhibitors.

Other names

FRS2αFGFR substrate 2FGFR-signaling adaptor SNTSNT-1SNT1FRS2AFRS2alphaFGFR signalling adaptor SNTSuc1-associated neurotrophic factor target 1FRS1ASNTepididymis secretory sperm binding protein

Not directly targeted by drugs. FGFR inhibitors block activation of FGFR, thereby preventing tyrosine phosphorylation of FRS2 and downstream signal propagation.