| First Author | Clark JF | Year | 2023 |
| Journal | Biol Open | Volume | 12 |
| Issue | 7 | PubMed ID | 37421147 |
| Mgi Jnum | J:338808 | Mgi Id | MGI:7515129 |
| Doi | 10.1242/bio.059942 | Citation | Clark JF, et al. (2023) FRS2-independent GRB2 interaction with FGFR2 is not required for embryonic development. Biol Open 12(7) |
| abstractText | FGF activation is known to engage canonical signals, including ERK/MAPK and PI3K/AKT, through various effectors including FRS2 and GRB2. Fgfr2FCPG/FCPG mutants that abrogate canonical intracellular signaling exhibit a range of mild phenotypes but are viable in contrast to embryonic lethal Fgfr2-/- 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 that Fgfr2T/T mice 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 the T mutation on the sensitized FCPG background but found that Fgfr2FCPGT/FCPGT mutants 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. |
