From pathway to population – a multiscale model of juxtacrine EGFR-MAPK signalling

Walker, DC; Georgopoulos, NT; Southgate, J

doi:10.1186/1752-0509-2-102

BMC Systems Biology

Table 3 Intracellular pathway model. Rate equations relating to intracellular EGFR-MAPK pathway.

From: From pathway to population – a multiscale model of juxtacrine EGFR-MAPK signalling

	Species	Rate equation	Constants
11	Shc	$\frac{d[Shc]}{dt} = - k_{5} \sum_{c nt = 1}^{na} [RP] {[Shc]/(K}_{5} + [Shc]) + V_{6} {[Shc-P]/(K}_{6} + [ShcP])$	k₅ = 12 K₅ = 6 × 10³
12	ShcP	$\begin{array}{l} \frac{d[ShcP]}{dt} = \frac{k_{5} \sum_{c nt = 11}^{na} [RP] [Shc]}{K_{5} + [Shc]} - \frac{V_{6} [ShcP]}{K_{6} + [ShcP]} - k_{7} [ShcP][GrbSos] \\ + k_{- 7} [ShcGrbSos] + \frac{k_{8} [ErkPP][ShcGrbSos]}{K_{8} + [ShcGrbSos]} \end{array}$	V₆= 3.0 × 10⁵ K₆ = 6 × 10³ K₇ = 2 × 10^-3 k_-7 = 3.81
13	GrbSos	$\frac{d[GrbSos]}{dt} = - k {}_{7}{[ShcP]} [GrbSos] + k_{- 7} [ShcGrbSos] + \frac{V_{9} [GrbSosP]}{{(K}_{9} + [GrbSosP]}$	K₈ = 1.6; K₈ = 6 × 10⁵
14	GrbSosP	$\frac{d[GrbSosP]}{dt} = \frac{k_{8} [ErkPP][ShcGrbSos]}{K_{8} + [ShcGrbSos]} - \frac{V_{9} [GrbSosP]}{K_{9} + [GrbSosP]}$	V₉ = 75; K₉ = 2.0 × 10⁴
15	ShcGrbSos	$\begin{array}{l} \frac{d[ShcGrbSos]}{dt} = k {}_{7}{[ShcP]} [GrbSos] - k_{- 7} [ShcGrbSos] - \frac{k_{8} [ErkPP][ShcGrbSos]}{K_{8} + [ShcGrbSos]} \\ - k_{10} [R a s G D P] [S h c G r b S o s] + k_{- 10} [S h c G r b S o s R a s] + k_{11} [S h c G r b S o s R a s] \end{array}$	k₁₀ = 1.63 × 10^-2 k₁₀ = 10 k₁₁ = 15
16	RasGDP	$\frac{d[RasGDP]}{dt} = - k_{10} [R a s G D P] [S h c G r b S o s] + k_{- 10} [S h c G r b S o s R a s] + k_{13} [R a s G A P]$	k₁₂ = 5.0 × 10^-3 k_-12 = 60
17	ShcGrbSosRas	$\frac{d[ShcGrbSosRas]}{dt} = k_{10} [R a s G D P] [S h c G r b S o s] - k_{- 10} [S h c G r b S o s R a s] - k_{11} [S h c G r b S o s R a s]$	k₁₃ = 7.2 × 10² k₁₄ = 1.2 × 10^-3
18	RasGTP	$\begin{array}{l} \frac{d[RasGTP]}{dt} = k_{- 11} [ShcGrbSosRas] - k_{12} [RasGTP] [GAP] + \\ k_{- 12} [RasGAP] - k_{14} [Raf][RasGTP] + k_{- 14} [RasRaf ] + k_{15} [RasRaf] \end{array}$	k_-14 = 3.0 k₁₅ = 27
19	GAP	$\frac{dGAP]}{dt} = - k_{12} [RasGTP][GAP] + k_{- 12} [RasGAP] + k_{13} [R a s G A P]$	V₁₆ = 9.7 × 10⁴ K₁₆ = 6 × 10³
20	RasGAP	$\frac{d[RasGAP]}{dt} = k_{12} [RasGTP][GAP] - k_{- 12} [RasGAP] - k_{13} [R a s G A P]$	k₁₇ = 50; K₁₇ = 9 × 10³
21	Raf	$\frac{d[Raf]}{dt} = - k_{14} [RafP][RasGTP] + k_{- 14} [RasRaf] + \frac{V_{16} [R a f P]}{K_{16} + [R a f P]}$	V₁₈ = 9.2 × 10⁵ K₁₈ = 6 × 10⁵
22	RasRaf	$\frac{dRasRaf]}{dt} = k_{14} [RafP][RasGTP] - k_{- 14} [RasRaf] - k_{15} [R a s R a f]$	k₁₉ = 50; K₁₉ = 9 × 10³
23	RafP	$\frac{d[RafP]}{dt} = k_{15} [R a s R a f] - \frac{V_{16} [R a f P]}{K_{16} + [R a f P]}$	V₂₀ = 9.2 × 10⁵ K₂₀ = 6 × 10⁵
24	Mek	$\frac{d[Mek]}{dt} = \frac{- k_{17} [RafP][Mek]}{K_{17} + [Mek]} + \frac{V_{18} [M e k P]}{K_{18} + [M e k P]}$	k₂₁ = 8.3; K₂₁ = 9 × 10⁴
25	MekP	$\frac{d[MekP]}{dt} = \frac{k_{17} [RafP][Mek]}{K_{17} + [Mek]} - \frac{V_{18} [M e k P]}{K_{18} + [M e k P]} \frac{- k_{19} [RafP] [MekP]}{K_{19} + [MekP]} + \frac{V_{20} [M e k P P]}{K_{20} + [M e k P P]}$	V₂₂ = 2.0 × 10⁵
26	MekPP	$\frac{d[MekPP]}{dt} = \frac{k_{19} [RafP][MekP]}{K_{19} + [MekP]} - \frac{V_{20} [M e k P P]}{K_{20} + [M e k P P]}$	K₂₂ = 6 × 10⁵ k₂₃ = 8.3;
27	Erk	$\frac{d[Erk]}{dt} = \frac{- k_{21} ([MekP] + [MekPP]) [Erk]}{K_{21} + [E r k]} + \frac{V_{22} [E r k P]}{K_{22} + [E r k P]}$	K₂₃ = 9 × 10⁴
28	ErkP	$\begin{array}{l} \frac{d[ErkP]}{dt} = \frac{k_{21} ([MekP] + [MekPP]) .[Erk]}{K_{21} + [E r k]} - \frac{V_{22} [E r k P]}{K_{22} + [E r k P]} \\ - \frac{k_{23} ([MekP] + [MekPP]) .[ErkP]}{K_{23} + [E r k P]} + \frac{V_{24} [E r k P P]}{K_{24} + [E r k P P]} \end{array}$	V₂₄ = 4.0 × 10⁵; K₂₄ = 6 × 10⁵
29	ErkPP	$\frac{d[ErkPP]}{dt} = \frac{k_{23} ([MekP] + [MekPP]) .[ErkP]}{K_{23} + [E r k P]} - \frac{V_{24} [E r k P P]}{K_{24} + [E r k P P]}$

Units are as for Table 1. All constants are taken directly from [14].

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