Download - The EGFR Signaling Pathway
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The EGFR Signaling Pathway
+EGF
Epidermal Growth Factor (EGF) Binds to Epidermal Growth Factor Receptor (EGFR) Results in
Cell Growth Cell Proliferation Cell Differentiation
Controls through the EGFR signaling pathway
+ Mouse EGF
From Wikipedia
+The EGFR Signaling PathwayOverview
+The EGFR Signaling Pathway
Binds to EGF Controls:
signaling adapter proteins:accessory proteins, lack intrinsic enzymatic activity,
mediate specific protein-protein interactions that drive the formation of protein complexes
Grb2 Shc
Enzyme PLCΥ Guanine nucleotide exchange factor: Sos
Overview
+The EGFR Signaling Pathway
Molecules EGF R: Unbounded EGFR Ra: Bounded EGFR R2: Dimeric EGFR
Reactions
1. EGF binds to monomeric EGFR
2. EGF-bounded EGFRs dimerize
Binding of EGF
+The EGFR Signaling Pathway
# Ligand-receptor binding
egfr(l,r) + egf(r) <-> egfr(l!1,r).egf(r!1) kp1, km1
# Receptor-aggregation
egfr(l!1,r) + egfr(l!2,r) <-> egfr(l!1,r!3).egfr(l!2,r!3) kp2,km2
Binding of EGF
+The EGFR Signaling Pathway
Molecules R2: Dimeric EGFR RP: Transphosphorylated
EGFR
Reactions
3. Dimeric EGFR transphosphorylation
4. Dimeric EGFR dephosphorylation
Transphosphorylation of EGFR
+The EGFR Signaling Pathway
# Transphosphorylation of egfr
egfr(r!1,Y1068~Y) -> egfr(r!1,Y1068~pY) kp3
egfr(r!1,Y1148~Y) -> egfr(r!1,Y1148~pY) kp3
#Dephosphorylayion
egfr(Y1068~pY) -> egfr(Y1068~Y) km3
egfr(Y1148~pY) -> egfr(Y1148~Y) km3
Transphosphorylation of EGFR
+The EGFR Signaling Pathway
Not Included in the BNGL File
Molecules PLCΥ PLCΥP: Phosphorylated PLCΥ RP: EGFR
transphosphorylated at Y992
Reactions
5. Binding of PLCΥ
6. Phosphorylation of PLCΥ
7. Binding of PLCΥP to RP at Y992
Binding of PLCγ
+The EGFR Signaling Pathway
Molecules Grb2 RP: EGFR
transphosphorylated at Y1068
Reactions
9. Binding of Grb2 to RP at Y1068
10. Binding of Sos to pY1068-Grb2
11. Binding of PLCΥP to RP at 1068
Binding of Grb2
+The EGFR Signaling Pathway
# Y1068 activity
egfr(Y1068~pY) + Grb2(SH2,SH3) <-> egfr(Y1068~pY!1).Grb2(SH2!1,SH3) kp9,km9
egfr(Y1068~pY) + Grb2(SH2,SH3!2) <-> egfr(Y1068~pY!1).Grb2(SH2!1,SH3!2) kp11,km11
egfr(Y1068~pY!1).Grb2(SH2!1,SH3) + Sos(dom) <-> egfr(Y1068~pY!1).Grb2(SH2!1,SH3!2).Sos(dom!2) kp10,km10
Binding of Grb2
+The EGFR Signaling Pathway
Molecules Shc ShcP: Phosphorylated Shc RP: EGFR transphosphorylated
at Y1148/74
Reactions
13. Binding of Shc to pY1148/74
14. Phosphorylation of Shc
15. Binding of ShcP to pY1148/74
17. Binding of Grb2 to pY1148/74-ShcP
Binding of Shc
+The EGFR Signaling Pathway
# Rule 13
egfr(Y1148~pY) + Shc(PTB,Y317~Y) <-> egfr(Y1148~pY!1).Shc(PTB!1,Y317~Y) kp13,km13
# Rule 14
egfr(r!2,Y1148~pY!1).Shc(PTB!1,Y317~Y) -> egfr(r!2,Y1148~pY!1).Shc(PTB!1,Y317~pY) kp14
# Rule 15
egfr(Y1148~pY) + Shc(PTB,Y317~pY) <-> egfr(Y1148~pY!1).Shc(PTB!1,Y317~pY) kp15,km15
# Rule 17
egfr(Y1148~pY!1).Shc(PTB!1,Y317~pY) + Grb2(SH2,SH3) <-> egfr(Y1148~pY!1).Shc(PTB!1,Y317~pY!2).Grb2(SH2!2,SH3) kp17,km17
Binding of Shc
+The EGFR Signaling Pathway
Reactions
18. Binding of ShcP-Grb2 to pY1148/74
19. Binding of Sos to pY1148/74-ShcP-Grb2
20. Binding of ShcP-Grb2-Sos to pY1148/74
24. Binding of Grb2-Sos to pY1148/74-ShcP
Binding of Shc
+The EGFR Signaling Pathway
# Rule 18
egfr(Y1148~pY) + Shc(PTB,Y317~pY!1).Grb2(SH2!1,SH3) <-> egfr(Y1148~pY!2).Shc(PTB!2,Y317~pY!1).Grb2(SH2!1,SH3) kp18,km18
# Rule 19, note the pattern matching here
Shc(PTB!1,Y317~pY!2).Grb2(SH2!2,SH3) + Sos(dom) <-> Shc(PTB!1,Y317~pY!2).Grb2(SH2!2,SH3!3).Sos(dom!3) kp19,km19
# Rule 20
egfr(Y1148~pY) + Shc(PTB,Y317~pY!1).Grb2(SH2!1,SH3!3).Sos(dom!3) <-> egfr(Y1148~pY!2).Shc(PTB!2,Y317~pY!1).Grb2(SH2!1,SH3!3).Sos(dom!3) kp20,km20
# Rule 24
egfr(Y1148~pY!1).Shc(PTB!1,Y317~pY) + Grb2(SH2,SH3!3).Sos(dom!3) <-> egfr(Y1148~pY!1).Shc(PTB!1,Y317~pY!2).Grb2(SH2!2,SH3!3).Sos(dom!3) kp24,km24
Binding of Shc
+The EGFR Signaling Pathway
Reactions
12. Binding of Grb2 and Sos
23. Binding of Grb2-Sos to ShcP
24. Binding of ShcP-Grb2 to Sos
25. Binding of ShcP and Grb2
26. Dephoshporylation of ShcP
27. Dephoshphorylation of PLCΥ(Not Included)
25. Inactivation of PLCΥP (Not Included)
Cytosolic Reactions without EGFR
+The EGFR Signaling Pathway
# Rule 12
Grb2(SH2,SH3) + Sos(dom) <-> Grb2(SH2,SH3!1).Sos(dom!1) kp12,km12
# Rule 23
Shc(PTB,Y317~pY) + Grb2(SH2,SH3!2) <-> Shc(PTB,Y317~pY!1).Grb2(SH2!1,SH3!2) kp23,km23
# Rule 22
Shc(PTB,Y317~pY!2).Grb2(SH2!2,SH3) + Sos(dom) <-> Shc(PTB,Y317~pY!2).Grb2(SH2!2,SH3!3).Sos(dom!3) kp22,km22
# Rule 21
Shc(PTB,Y317~pY) + Grb2(SH2,SH3) <-> Shc(PTB,Y317~pY!1).Grb2(SH2!1,SH3) kp21,km21
# Rule 16
Shc(PTB,Y317~pY) -> Shc(PTB,Y317~Y) km16
Cytosolic Reactions without EGFR
+The EGFR Signaling PathwayPutting all together
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+The ENDThank You!
