NTRK2 activates RAS signaling through FRS2

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).

FRS2（FRS2蛋白）参与TRKB介导的RAS信号通路激活。其具体作用机制尚未阐明。推测SOS1（SOS1蛋白），与GRB2（GRB2蛋白）形成复合物，通过磷酸化的FRS2被招募至激活的NTRK2（TRKB受体），进而催化RAS（HRAS、KRAS或NRAS）上的鸟苷酸交换，导致活性RAS:GTP复合物的形成，并启动RAS/RAF/MAPK信号通路。PTPN11（SHP2蛋白）通过促进FRS2介导的RAS信号通路在NTRK2下游的激活，可能通过参与GRB2的招募（Easton等，1999，Easton等，2006）实现。