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Text S1. Additional information of the in silico MAPK model
To check the robustness of inferring systemic impact, we derived alternative parameter sets based on the FRET data measured by Fujioka et al. ADDIN EN.CITE Fujioka200625[1]252517Fujioka, A. Terai, K. Itoh, R. E. Aoki, K. Nakamura, T. Kuroda, S. Nishida, E. Matsuda, M. Dynamics of the Ras/ERK MAPK cascade as monitored by fluorescent probes.J Biol Chem. J Biol Chem.8917-89262812006[ HYPERLINK \l "_ENREF_1" \o "Fujioka, 2006 #25" 1]:
Parameter set 1 (derived from initial concentrations of ShcGS, Ras, Raf, Mek and Erk measured by Fujioka et al.):
Initial concentrations ( M ) :
S h c G S = 0 . 4 ; R a s G D P = 0 . 4 ; R a s G T P = 0 ; R a f = 0 . 0 1 3 , R a f * = 0 ; M e k = 1 . 4 ; M e k * = 0 ; E r k = 0 . 9 6 ; E r k * = 0
R a t e c o n s t a n t s ( M m i n - 1 ) :
c 2 = 3 8 . 5 ; c 6 = 2 . 7 3 ; c 8 = 0 . 5 1 ; c 1 0 = 1 5 ; c 1 2 = 3 . 1 5
R a t e c o n s t a n t s ( M ) :
c 7 = 0 . 3 5 ; c 9 = 0 . 7 7 ; c 1 1 = 0 . 0 3
R a t e c o n s t a n t s ( m i n - 1 ) :
c 1 = 6 9 ; c 3 = 1 4 ; c 4 = 1 0 7 . 7 ; c 5 = 0 . 7 8
P a r a m e t e r s e t 2 ( o p t i m i z e d b a s e d o n t h e t i m e c o u r s e d a t a f r o m F u j i o k a e t a l . , w i t h i n i t i a l c o n c e n t r a t i o n s o f S h c G S , R a s , R a f , M e k a n d E r k m e a s u r e d b y F u j i o k a e t a l . ) :
I n i t i a l c o n c e n t r a t i o n s ( M ) :
S h c $ ' 0 1 ; < Q R S ϻ𦕃tbTbA %hL] CJ OJ PJ QJ aJ mH nH uhL] CJ OJ PJ QJ aJ #j hL] CJ OJ PJ QJ UaJ hL] 6CJ OJ PJ QJ aJ #hJ hL] 6CJ OJ PJ QJ aJ hu hL] CJ OJ PJ QJ aJ )hX'y hL] 6CJ OJ PJ QJ \]aJ &hu hL] 56CJ OJ PJ QJ aJ #hu hL] 5CJ OJ PJ QJ aJ hUy 5CJ OJ PJ QJ aJ hL] 5CJ OJ PJ QJ aJ < =
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պըweQeQ;Qe *h+: hL] 6CJ H*KH OJ QJ ^J aJ &h+: hL] 6CJ OJ QJ \^J aJ #h+: hL] 6CJ OJ PJ QJ aJ hL] CJ OJ PJ QJ aJ #hJ hL] 6CJ OJ PJ QJ aJ hu hL] CJ OJ PJ QJ aJ #j hL] CJ OJ PJ QJ UaJ 4j hL] CJ OJ PJ QJ UaJ mH nH u %hL] CJ OJ PJ QJ aJ mH nH u.j hL] CJ OJ PJ QJ UaJ mH nH u , 0 @ B D V X \ l r 0 2 B D Z ^ l ذذ؉whw hL] 6CJ OJ PJ QJ aJ #hJ hL] 6CJ OJ PJ QJ aJ hu hL] CJ OJ PJ QJ aJ *h+: hL] 6CJ H*KH OJ QJ ^J aJ &h+: hL] 6CJ OJ QJ \^J aJ 'h+: hL] 6CJ KH OJ PJ QJ aJ #h+: hL] 6CJ OJ PJ QJ aJ *h+: hL] 6CJ H*KH OJ PJ QJ aJ & . 0 2 F H L ` f t
! " . 0 7 ϻϹϻύύyύyύύyϻύύύϹϻύύύύ 'h+: hL] 6CJ KH OJ PJ QJ aJ *h+: hL] 6CJ H*KH OJ PJ QJ aJ *h+: hL] 6CJ H*KH OJ QJ ^J aJ U&h+: hL] 6CJ OJ QJ \^J aJ #h+: hL] 6CJ OJ PJ QJ aJ hu hL] CJ OJ PJ QJ aJ hL] CJ OJ PJ QJ aJ .G S = 0 . 4 ; R a s G D P = 0 . 4 ; R a s G T P = 0 ; R a f = 0 . 0 1 3 , R a f * = 0 ; M e k = 1 . 4 ; M e k * = 0 ; E r k = 0 . 9 6 ; E r k * = 0
R a t e c o n s t a n t s ( M m i n - 1 ) :
c 2 = 0 . 8 2 ; c 6 = 5 . 0 2 ; c 8 = 2 0 . 7 3 ; c 1 0 = 3 3 . 9 ; c 1 2 = 0 . 5 4
R a t e c o n s t a n t s ( M ) :
c 7 = 7 0 . 3 ; c 9 = 2 0 . 2 7 ; c 1 1 = 0 . 9 6
R a t e c o n s t a n t s (min-1):
c1 = 27.32; c3 = 2.14; c4 = 187.15; c5 = 16.08
References:
1. Fujioka A, Terai K, Itoh RE, Aoki K, Nakamura T, et al. (2006) Dynamics of the Ras/ERK MAPK cascade as monitored by fluorescent probes. J Biol Chem 281: 8917-8926.
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