FRS2 is involved in TRKB-mediated activation of RAS signaling. The exact mechanism has not been elucidated. It is likely that SOS1, in complex with GRB2, recruited to activated NTRK2 (TRKB) receptor through phosphorylated FRS2, catalyzes guanine nucleotide exchange on RAS (HRAS, KRAS or NRAS), resulting in formation of the active RAS:GTP complex and initiation of RAS/RAF/MAPK signaling. PTPN11 (SHP2) facilitates FRS2-mediated activation of RAS downstream of NTRK2, possibly by contributing to GRB2 recruitment (Easton et al. 1999, Easton et al. 2006).
guanyl-nucleotide exchange factor activity of BDNF,NTF4:p-5Y-NTRK2:p-Y-FRS2:GRB2-1:SOS1 [plasma membrane]
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