Fibroblast growth factor receptor substrate 3 (FRS3)

Fibroblast growth factor receptor substrate 3 (FRS3) is an adapter protein localized to the peripheral plasma membrane that serves as a critical link in transducing signals from activated fibroblast growth factor receptors (FGFRs) to intracellular effectors, particularly the MAPK (Mitogen-Activated Protein Kinase) and PI3K/AKT pathways[1][3][6]. Upon FGFR stimulation, FRS3 becomes tyrosine phosphorylated, subsequently recruiting downstream signaling components such as GRB2 and Gab1, and modulating diverse cellular functions including differentiation and proliferation[1][3]. FRS3 is especially important in mediating FGFR1 function during neuronal development and can also participate in signaling from neurotrophin receptors such as NTRK1-3[3]. While it shares structural and functional similarity with FRS2, FRS3 has distinct, context-dependent roles, particularly in the negative regulation of ERK2 activity and in certain cancer types including thyroid and prostate cancer[3][6]. Defects or dysregulation in FRS3-mediated signaling have been implicated in cancer pathogenesis and developmental disorders such as Kallmann syndrome and multiple endocrine neoplasia[1][2][6]. Notes: - FRS3 is considered an adaptor/scaffold protein, not a receptor or enzyme itself; thus, it does not have known drug ligands or approved therapies targeting it directly as of current knowledge[3][6]. - There are closely related paralogs such as FRS2 (also known as SNT-1 or FRS2-alpha)[1][3]. - Contextual data (e.g., kidney, neuronal, or endocrine development) suggest roles in highly regulated developmental pathways and malignancy[1][3][6].

Other names

FRS3FRS2BFRS2-betaFRS2betaSNT-2SNT2FGFR substrate 3FGFR-signaling adaptor SNT2Suc1-associated neurotrophic factor target 2testicular tissue protein Li 71

Adapter or scaffold for FGFR, transmitting signals to MAPK/ERK and PI3K/AKT pathways; required for FGFR1-mediated signaling; mediates signal transduction from select neurotrophin receptors (e.g., NTRK1, NTRK2, NTRK3)