FRS2-independent GRB2 interaction with FGFR2 is not required for embryonic development

Abstract

AbstractFGF activation is known to engage canonical signals, including ERK/MAPK and PI3K/AKT, through various effectors including FRS2 and GRB2.Fgfr2FCPG/FCPGmutants that abrogate canonical intracellular signaling exhibit a range of mild phenotypes but are viable in contrast to embryonic lethalFgfr2-/-mutants. GRB2 has been reported to interact with FGFR2 through a non-traditional mechanism, by binding to the C-terminus of FGFR2 independently of FRS2 recruitment. To investigate if this interaction provides functionality beyond canonical signaling, we generated mutant mice harboring a C-terminal truncation (T). We found thatFgfr2T/Tmice are viable and have no distinguishable phenotype, indicating that GRB2 binding to the C-terminal end of FGFR2 is not required for development or adult homeostasis. We further introduced theTmutation on the sensitizedFCPGbackground but found thatFgfr2FCPGT/FCPGTmutants did not exhibit significantly more severe phenotypes. We therefore conclude that, while GRB2 can bind to FGFR2 independently of FRS2, this binding does not have a critical role in development or homeostasis.