FGF pathway map

Pi-calculus model containing processes FGF, FGFR, FRS2, Plc, Src, Spry, Cbl, Grb, Shp and Sos (model extension with Src positive feedback here)


These reactions approximate the behaviour of the FGF pathway (see SBML for the full model).
1. FGF binds to FGFR
       FGF+FGFR ↔ FGFR:FGF (kon=5e+6 M-1s-1, koff=5e-3 s-1)

2. Whilst FGFR:FGF exists
       FGFR Y653/Y654 → FGFR Y653P/Y654P (kcat=0.013s-1)
3. When FGFR Y653P/Y654P
       FGFR Y766 → FGFR Y766P (kcat=0.004s-1)

4. FGFR binds FRS2
       FGFR+ FRS2 ↔ FGFR:FRS2 (kon=2.5e+6 M-1s-1, koff=5e-2 s-1)

5. When FGFR Y653P/Y654P and FGFR:FRS2
       FRS2 Y196 → FRS2 Y196P (kcat=0.005s-1)
       FRS2 Y306 → FRS2 Y306P (kcat=0.005s-1)
       FRS2 Y471 → FRS2 Y471P (kcat=0.005s-1)

6. Reverse when Shp2 bound to FRS2:
       FRS2 Y196P → FRS2 Y196 (kcat=12s-1)
       FRS2 Y306P → FRS2 Y306 (kcat=12s-1)
       FRS2 Y471P → FRS2 Y471 (kcat=12s-1)
7. FRS2 effectors bind phosphoFRS2:
       Src+FRS2 Y196P ↔ Src:FRS2 Y196P (kon=2.5e+6 M-1s-1, koff=5e-2 s-1)
       Grb2+FRS2 Y306P ↔ Grb2:FRS2 Y306P (kon=2.5e+6 M-1s-1, koff=5e-2 s-1)
       Shp2+FRS2 Y471P ↔ Shp2:FRS2 Y471P (kon=2.5e+6 M-1s-1, koff=5e-2 s-1)

8. When Src:FRS2 we relocate/remove
       Src:FRS2 → relocate out (t1/2 = 15min)

9. When Plc:FGFR it degrades FGFR
       PLC+FGFR Y766 ↔ PLC:FGFR Y766 (kon=2.5e+6 M-1s-1, koff=5e-2 s-1)
       PLC:FGFR Y766 → degFGFR (t1/2 = 60 min)

10. Spry appears in time dependent manner:
       → Spry (t = 20min)

11. Spry binds Src and is phosphorylated:
       Spry+Src ↔ Spry Y55:Src (kon=1e+5 M-1s-1, koff=1e-2 s-1)
       Spry Y55:Src → Spry Y55P:Src (kcat=10s-1)
       Spry Y55P+Src ↔ Spry Y55P:Src (kon=1e+5 M-1s-1, koff=1e-4 s-1)
       Spry Y55P+Cbl ↔ Spry Y55P:Cbl (kon=1e+5 M-1s-1, koff=1e-4 s-1)
       Spry Y55P+Grb2 ↔ Spry Y55P:Grb2 (kon=2.5e+6 M-1s-1, koff=5e-2 s-1)

12. phosphoSpry binds Cbl which degrades/removes FRS2
       Spry Y55P:Cbl+FRS2-Ubi → FRS2-Ubi (t1/2 = 25min)

13. Spry is dephosphorylated by Shp2: (when Shp2 bound to FRS2)
       Spry Y55P → Spry Y55 (kcat=12s-1)
14. Grb2 binds Sos
       Grb2+Sos ↔ Grb2:Sos (kon=1e+5 M-1s-1, koff=1e-4 s-1)