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

Area of Science:

• Cell Biology
• Molecular Biology
• Developmental Biology

Background:

• Fibroblast Growth Factor (FGF) signaling is crucial for cellular processes, primarily mediated by canonical pathways like ERK/MAPK and PI3K/AKT.
• FGFR2 mutations affecting canonical signaling result in mild phenotypes, contrasting with embryonic lethal mutations, suggesting alternative signaling mechanisms.

Approach:

• Generated mutant mice with a C-terminal truncation (T) in FGFR2 to investigate GRB2 binding independently of FRS2.
• Assessed the developmental and homeostatic roles of this non-canonical GRB2-FGFR2 interaction in mice.
• Introduced the truncation mutation onto a sensitized FCPG background to identify potential synergistic effects.

Key Points:

• Mice with the FGFR2 C-terminal truncation (Fgfr2 T) were viable and showed no discernible phenotype.
• GRB2 binding to the FGFR2 C-terminus is not required for normal development or adult homeostasis.
• The T mutation did not significantly exacerbate phenotypes on the sensitized FCPG background.

Conclusions:

• The non-canonical interaction between GRB2 and the FGFR2 C-terminus, independent of FRS2, does not play a critical role in mouse development or homeostasis.
• This finding clarifies the functional significance of alternative signaling pathways in FGF receptor signaling.