Appendix 1—table 1. Equations used in the mathematical model.

L-EGFR: ligand-bound EGFR; EGFR:EGFR: EGFR in dimeric form; EGFR: EGFR bound to ZtSH2.

Species	Notation	Equation
Soluble ligand (L)	N 1	${\displaystyle \frac{d{N}_1}{dt}=0}$ (A1)
Unbound ZtSH2 (*)	N 2	${\displaystyle \frac{d{N}_2}{dt}=-k_8{N}_2\ast \left(2N_6+2N_7+N_9+N_{10}+N_{11}\right)+k_9\ast \left(N_8+N_9+N_{10}+N_{11}+2N_{12}+2N_{13}+2N_{14}+N_{15}+N_{16}\right)}$ (A2)
EGFR	N 3	${\displaystyle \frac{d{N}_3}{dt}=-k_1{N}_3{N}_1+k_2{N}_4-2k_5{N}_3^2-k_5{N}_3{N}_4-k_5{N}_3{N}_{15}-k_5{N}_3{N}_{16}+2k_6{N}_5+k_6{N}_8+k_7{N}_6+k_7{N}_9+k_9{N}_{15}}$ (A3)
L-EGFR	N 4	${\displaystyle \frac{d{N}_4}{dt}=k_1{N}_3{N}_1-k_2{N}_4-k_5{N}_3{N}_4-2k_5{N}_4^2-k_5{N}_4{N}_{15}-k_5{N}_4{N}_{16}+k_7{N}_6+k_7{N}_{10}+2k_7{N}_7+k_7{N}_{11}+k_9{N}_{16}}$ (A4)
EGFR:EGFR	N 5	$\frac{d{N}_5}{dt}={-2k}_1{N}_5{N}_1+k_3{N}_6+k_5{N}_3^2-k_6{N}_5+k_9{N}_8$ (A5)
L-EGFR:EGFR	N 6	${\displaystyle \frac{d{N}_6}{dt}=-k_1{N}_6{N}_1+2k_4{N}_7+2k_1{N}_5{N}_1-k_3{N}_6+k_5{N}_3{N}_4-k_7{N}_6-2k_8{N}_6{N}_2+k_9{N}_9+k_9{N}_{10}}$ (A6)
L-EGFR:L-EGFR	N 7	$\frac{d{N}_7}{dt}=k_5{N}_6{N}_1{-2k}_4{N}_7+k_5{N}_4^2{-k}_7{N}_7-{2k}_8{N}_7{N}_2+k_9{N}_{11}$ (A7)
EGFR*:EGFR	N 8	$\frac{d{N}_8}{dt}=-2k_1{N}_8{N}_1+k_3{N}_9+k_3{N}_{10}+k_5{N}_3{N}_{15}-k_6{N}_8-k_9{N}_8+{2k}_9{N}_{12}$ (A8)
L-EGFR*:EGFR	N 9	$\frac{d{N}_9}{dt}=k_1{N}_8{N}_1-k_1{N}_9{N}_1-k_3{N}_9+k_4{N}_{11}+k_5{N}_3{N}_{16}-k_7{N}_9+k_8{N}_6{N}_2-k_8{N}_9{N}_2-k_9{N}_9+k_9{N}_{13}$ (A9)
L-EGFR:EGFR*	N 10	$\frac{d{N}_{10}}{dt}=k_1{N}_8{N}_1-k_3{N}_{10}-k_1{N}_{10}{N}_1+k_4{N}_{11}+k_5{N}_4{N}_{15}-k_7{N}_{10}+k_8{N}_6{N}_2-k_9{N}_{10}-k_8{N}_{10}{N}_2+k_9{N}_{13}$ (A10)
L-EGFR*:L-EGFR	N 11	$\frac{d{N}_{11}}{dt}=k_1{N}_9{N}_1-{2k}_4{N}_{11}+k_1{N}_{10}{N}_1+k_5{N_{4}N}_{16}-k_7{N}_{11}+{2k}_8{N}_7{N}_2-k_9{N}_{11}-k_8{N}_{11}{N}_2+{2k}_9{N}_{14}$ (A11)
EGFR*:EGFR*	N 12	$\frac{d{N}_{12}}{dt}=-{2k}_1{N}_{12}{N}_1+k_3{N}_{13}+k_5{N}_{15}^2-k_6{N}_{12}-{2k}_9{N}_{12}$ (A12)
L-EGFR*:EGFR*	N 13	$\frac{d{N}_{13}}{dt}={2k}_1{N}_{12}{N}_1-k_3{N}_{13}-k_1{N}_{13}{N}_1+{2k}_4{N}_{14}+k_5{N}_{15}{N}_{16}-k_7{N}_{13}+k_8{N}_9{N}_2-2k_9{N}_{13}+k_8{N}_{10}{N}_2$ (A13)
L-EGFR*:L-EGFR*	N 14	$\frac{d{N}_{14}}{dt}=k_1{N}_{13}{N}_1-{2k}_4{N}_{14}+k_5{N}_{16}^2-k_7{N}_{14}+k_8{N}_{11}{N}_2-{2k}_9{N}_{14}$ (A14)
EGFR*	N 15	$\frac{d{N}_{15}}{dt}={-k}_1{N}_{15}{N}_1+k_2{N}_{16}-2k_5{N}_{15}^2+2k_6{N}_{12}-k_5{N_{3}N}_{15}+k_6{N}_8-k_5{N}_{15}{N}_{16}+k_7{N}_{13}-k_5{N_{4}N}_{15}+k_7{N}_{10}-k_9{N}_{15}$ (A15)
L-EGFR*	N 16	$\frac{d{N}_{16}}{dt}=k_1{N}_{15}{N}_1-k_2{N}_{16}-2k_5{N}_{16}^2+2k_7{N}_{14}-k_5{N}_{15}{N}_{16}+k_7{N}_{13}-k_5{N}_{16}{N}_3+k_7{N}_9-k_5{N_{4}N}_{16}+k_7{N}_{11}-k_9{N}_{16}$ (A16)