Figure 3.

Loss of FGFR1 Signaling in BCs Leads to an Increase in Phosphorylation of Downstream Effector Proteins and a Decrease in Levels of a SPRY2 Isoform

(A) Schematic of in vitro experiment.

(B) Representative western blots from control and Fgfr1 cKO day-5 BCs showing pERK1/2, total ERK1/2, pAKT, total AKT, SPRY2, and histone H3.

(C) Quantification of protein in (B).

(D) Model. A major function of FGFR1 in BCs is to post-translationally modify SPRY2, resulting in a SPRY2 isoform which can negatively regulate the ERK/MAPK and AKT/PI3K pathways downstream of other RTKs.

(E) Confocal images of control Tg(KRT5-CreER); Rosa26R^fGFP/+ and cKO Tg(KRT5-CreER); Rosa26R^fGFP/+; Fgfr1^Δ/fx tracheal sections at 1.5 weeks after tmx administration showing an increase in pERK1/2 levels in the Fgfr1 cKO BCs. Green, GFP (reporter); red, pERK1/2 (active ERK1/2); blue, DAPI (nuclei). Scale bar, 25 μm.

(F) Schematic for exposure of wild-type BCs to FGF2.

(G) Representative western blots from day-6 FGF2-stimulated and control BCs showing SPRY2, pERK1/2, total ERK1/2, pAKT, total AKT, and histone H3.

(H) Quantification of protein levels in (G).

Error bars denote SEM. See also Figures S3–S5.