FRS2


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FRS2

A gene on chromosome 12q15 that encodes an adapter protein which links activated FGR and NGF receptors to downstream signalling pathways. FRS2 plays a key role in activating MAP kinases and in phosphorylating  PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, in response to ligand-mediated activation of FGFR1. FRS2 modulates signalling via SHC1 by competing with it for a common binding site on NTRK1. It is usually part of heteromultimeric protein complexes, and it is highly expressed in the heart, brain, spleen, lungs, liver, skeletal muscle, kidneys and testes.
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Next, we examined whether PD173074, a selective FGFR kinase inhibitor, affected FGFR1-mediated signaling pathways in RO82-W-1 cells in vitro by performing western blot analysis to evaluate the phosphorylation status of FGFR1 and its downstream effectors (i.e., FRS2, MEK, and ERK) (Figure 3(b)).
Lenvatinib inhibited the phosphorylation of FGFR1 and of FRS2, MEK, and ERK, in a concentration-dependent manner at a similar concentration to that at which it showed antiproliferative activity (3 [micro]M).
We hypothesis that this effect is due to the sequestering of adaptor proteins, such as FRS2, away from other proregenerative pathways, such as NGF-TRKA signalling.