// DOQCS : http://doqcs.ncbs.res.in/
// Accession Name = EGFR_Signaling_pathway
// Accession Number = 52
// Transcriber = Pradeep Kumar S, NCBS
// Developer = Kholodenko et al
// Species = Harlan Sprague Dawley rat; mammalian
// Tissue = Hepatocytes
// Cell Compartment = Cell membrane + cytosol
// Notes = This model is based on the model and parameters published in paper: Quantification of Short Term Signaling by the EGFR Kholodenko et al, The J Biol Chem. , Vol 274, No. 42, Issue of October 15, pp. 30169 - 30181, 1999.
Note: There are a few small ambiguities in the paper about initial conditions employed for obtaining the results. Thanks to Dr. Kholodenko for clarifying those ambiguities and providing the values used in the simulations:[G-S]=33.04579, [Grb]=51.95431, [SOS]=0.95421.
//genesis
// kkit Version 11 flat dumpfile
// Saved on Fri Dec 9 11:18:25 2005
include kkit {argv 1}
FASTDT = 0.0001
SIMDT = 0.001
CONTROLDT = 5
PLOTDT = 1
MAXTIME = 120
TRANSIENT_TIME = 2
VARIABLE_DT_FLAG = 0
DEFAULT_VOL = 1.6667e-21
VERSION = 11.0
setfield /file/modpath value /home2/bhalla/scripts/modules
kparms
//genesis
initdump -version 3 -ignoreorphans 1
simobjdump doqcsinfo filename accessname accesstype transcriber developer \
citation species tissue cellcompartment methodology sources \
model_implementation model_validation x y z
simobjdump table input output alloced step_mode stepsize x y z
simobjdump xtree path script namemode sizescale
simobjdump xcoredraw xmin xmax ymin ymax
simobjdump xtext editable
simobjdump xgraph xmin xmax ymin ymax overlay
simobjdump xplot pixflags script fg ysquish do_slope wy
simobjdump group xtree_fg_req xtree_textfg_req plotfield expanded movealone \
link savename file version md5sum mod_save_flag x y z
simobjdump geometry size dim shape outside xtree_fg_req xtree_textfg_req x y \
z
simobjdump kpool DiffConst CoInit Co n nInit mwt nMin vol slave_enable \
geomname xtree_fg_req xtree_textfg_req x y z
simobjdump kreac kf kb notes xtree_fg_req xtree_textfg_req x y z
simobjdump kenz CoComplexInit CoComplex nComplexInit nComplex vol k1 k2 k3 \
keepconc usecomplex notes xtree_fg_req xtree_textfg_req link x y z
simobjdump stim level1 width1 delay1 level2 width2 delay2 baselevel trig_time \
trig_mode notes xtree_fg_req xtree_textfg_req is_running x y z
simobjdump xtab input output alloced step_mode stepsize notes editfunc \
xtree_fg_req xtree_textfg_req baselevel last_x last_y is_running x y z
simobjdump kchan perm gmax Vm is_active use_nernst notes xtree_fg_req \
xtree_textfg_req x y z
simobjdump transport input output alloced step_mode stepsize dt delay clock \
kf xtree_fg_req xtree_textfg_req x y z
simobjdump proto x y z
simundump geometry /kinetics/geometry 0 1.6667e-24 3 sphere "" white black 9 \
-15 0
simundump geometry /kinetics/geometry[1] 0 8.3335e-25 3 sphere "" white black \
17 -15 0
simundump kpool /kinetics/RP 0 0 0 0 0 0 0 0 0.001 0 /kinetics/geometry grey \
black 3 -24 0
simundump kpool /kinetics/R2 0 0 0 0 0 0 0 0 0.001 0 /kinetics/geometry grey \
black 3 -18 0
simundump kpool /kinetics/enz4 0 0 0.001 0.001 1e-06 1e-06 0 0 0.001 0 \
/kinetics/geometry blue black 0 -21 0
simundump kenz /kinetics/enz4/r4 0 0 0 0 0 0.001 4.5e+07 1800 450 0 1 "" red \
blue "" 1 -21 0
simundump kreac /kinetics/r3 0 1 0.01 "" white black 5 -21 0
simundump kreac /kinetics/r2 0 10000 0.1 "" white black 0 -18 0
simundump kpool /kinetics/Ra 0 0 0 0 0 0 0 0 0.001 0 /kinetics/geometry grey \
black -3 -18 0
simundump kpool /kinetics/R 0 0 0.1 0.1 0.0001 0.0001 0 0 0.001 0 \
/kinetics/geometry grey black -4 -15 0
simundump kpool /kinetics/EGF 0 0 0.666 0.666 0.000666 0.000666 0 0 0.001 0 \
/kinetics/geometry white black -8 -15 0
simundump kreac /kinetics/r1 0 3000 0.06 "" white black -6 -18 0
simundump kpool /kinetics/R-PL 0 0 0 0 0 0 0 0 0.001 0 /kinetics/geometry \
blue black 11 -20 0
simundump kpool /kinetics/R-PLP 0 0 0 0 0 0 0 0 0.001 0 /kinetics/geometry \
blue black 14 -25 0
simundump kpool /kinetics/PLCrP 0 0 0 0 0 0 0 0 0.001 0 /kinetics/geometry \
blue black 11 -31 0
simundump kpool /kinetics/PLCr 0 0 0.105 0.105 0.000105 0.000105 0 0 0.001 0 \
/kinetics/geometry blue black 8 -25 0
simundump kreac /kinetics/r5 0 60000 0.2 "" white black 8 -22 0
simundump kreac /kinetics/r6 0 1 0.05 "" white black 14 -22 0
simundump kreac /kinetics/r7 0 0.3 6000 "" white black 14 -28 0
simundump kreac /kinetics/r25 0 1 0.03 "" white black 14 -33 0
simundump kpool /kinetics/PLCr-I 0 0 0 0 0 0 0 0 0.001 0 /kinetics/geometry \
blue black 14 -37 0
simundump kreac /kinetics/r13 0 90000 0.6 "" white black -7 -22 0
simundump kpool /kinetics/Shc 0 0 0.15 0.15 0.00015 0.00015 0 0 0.001 0 \
/kinetics/geometry blue black -2 -24 0
simundump kpool /kinetics/R-Sh 0 0 0 0 0 0 0 0 0.001 0 /kinetics/geometry \
blue black -11 -24 0
simundump kreac /kinetics/r14 0 6 0.06 "" white black -11 -27 0
simundump kpool /kinetics/R-ShP 0 0 0 0 0 0 0 0 0.001 0 /kinetics/geometry \
blue black -11 -30 0
simundump kreac /kinetics/r15 0 0.3 900 "" white black -7 -30 0
simundump kpool /kinetics/ShP 0 0 0 0 0 0 0 0 0.001 0 /kinetics/geometry blue \
black -2 -30 0
simundump kreac /kinetics/r17 0 3000 0.1 "" white black -11 -35 0
simundump kpool /kinetics/R-Sh-G 0 0 0 0 0 0 0 0 0.001 0 /kinetics/geometry \
blue black -11 -39 0
simundump kreac /kinetics/r19 0 10000 0.0214 "" white black -11 -43 0
simundump kpool /kinetics/R-Sh-G-S 0 0 0 0 0 0 0 0 0.001 0 /kinetics/geometry \
blue black -11 -47 0
simundump kreac /kinetics/r24 0 9000 0.0429 "" white black -15 -39 0
simundump kreac /kinetics/r18 0 0.3 900 "" white black -7 -39 0
simundump kreac /kinetics/r20 0 0.12 240 "" white black -7 -47 0
simundump kpool /kinetics/Sh-G-S 0 0 0 0 0 0 0 0 0.001 0 /kinetics/geometry \
52 black -2 -47 0
simundump kreac /kinetics/r22 0 30000 0.064 "" white black -2 -43 0
simundump kpool /kinetics/Sh-G 0 0 0 0 0 0 0 0 0.001 0 /kinetics/geometry \
blue black -2 -39 0
simundump kreac /kinetics/r21 0 3000 0.1 "" white black -2 -35 0
simundump kreac /kinetics/r23 0 0.1 21000 "" white black 1 -47 0
simundump kpool /kinetics/G-S 0 0 0.033046 0.033046 3.3046e-05 3.3046e-05 0 0 \
0.001 0 /kinetics/geometry blue black 4 -47 0
simundump kreac /kinetics/r11 0 0.03 4500 "" white black 7 -47 0
simundump kpool /kinetics/Grb 0 0 0.051954 0.051954 5.1954e-05 5.1954e-05 0 0 \
0.001 0 /kinetics/geometry blue black 4 -39 0
simundump kreac /kinetics/r9 0 3000 0.05 "" white black 7 -34 0
simundump kreac /kinetics/r12 0 0.0015 100 "" white black 4 -43 0
simundump kpool /kinetics/R-G 0 0 0 0 0 0 0 0 0.001 0 /kinetics/geometry blue \
black 10 -39 0
simundump kreac /kinetics/r10 0 10 0.06 "" white black 10 -43 0
simundump kpool /kinetics/SOS 0 0 0.00095421 0.00095421 9.5421e-07 9.5421e-07 \
0 0 0.001 0 /kinetics/geometry blue black 1 -51 0
simundump kpool /kinetics/R-G-S 0 0 0 0 0 0 0 0 0.001 0 /kinetics/geometry \
blue black 10 -47 0
simundump kpool /kinetics/enz8 0 0 0.001 0.001 1e-06 1e-06 0 0 0.001 0 \
/kinetics/geometry blue black 7 -29 0
simundump kenz /kinetics/enz8/r8 0 0 0 0 0 0.001 50000 4 1 0 1 "" red blue "" \
8 -29 0
simundump kpool /kinetics/enz16 0 0 0.001 0.001 1e-06 1e-06 0 0 0.001 0 \
/kinetics/geometry blue black 0 -27 0
simundump kenz /kinetics/enz16/r16 0 0 0 0 0 0.001 25000 6.8 1.7 0 1 "" red \
blue "" -2 -27 0
simundump kpool /kinetics/pEGFRtot 0 0 0 0 0 0 0 0 0.00050001 0 \
/kinetics/geometry[1] 2 yellow -17 -16 0
simundump kpool /kinetics/pShctot 0 0 0 0 0 0 0 0 0.001 0 /kinetics/geometry \
blue yellow -18 -30 0
simundump kpool /kinetics/Grb2_Shc 0 0 0 0 0 0 0 0 0.001 0 /kinetics/geometry \
53 yellow -17 -50 0
simundump kpool /kinetics/Shc_EGFR 0 0 0 0 0 0 0 0 0.001 0 /kinetics/geometry \
58 yellow -18 -42 0
simundump kpool /kinetics/Grb_EGFR 0 0 0 0 0 0 0 0 0.001 0 /kinetics/geometry \
23 yellow 12 -51 0
simundump kpool /kinetics/SOS_EGFR 0 0 0 0 0 0 0 0 0.001 0 /kinetics/geometry \
blue yellow -10 -51 0
simundump kpool /kinetics/pPLCr 0 0 0 0 0 0 0 0 0.001 0 /kinetics/geometry \
blue yellow 20 -29 0
simundump doqcsinfo /kinetics/doqcsinfo 0 db52.g EGFR_Signaling_pathway \
pathway "Pradeep Kumar S, NCBS" " Kholodenko et al" "citation here" \
" Harlan Sprague Dawley rat; mammalian" " Hepatocytes" \
" Cell membrane + cytosol" Qualitative \
"Quantification of Short Term Signaling by the EGFR Kholodenko et al, The J Biol Chem. , Vol 274, No. 42, Issue of October 15, pp. 30169 - 30181, 1999 ( peer-reviewed publication )" \
"Mathematically equivalent" "Approximates original data " 12 -13 0
simundump xgraph /graphs/conc1 0 0 119 0 148.78 0
simundump xgraph /graphs/conc2 0 0 68 0 22.716 0
simundump xplot /graphs/conc1/pEGFRtot.Co 3 524288 \
"delete_plot.w ; edit_plot.D " 2 0 0 1
simundump xplot /graphs/conc1/pShctot.Co 3 524288 \
"delete_plot.w ; edit_plot.D " blue 0 0 1
simundump xplot /graphs/conc1/Grb2_Shc.Co 3 524288 \
"delete_plot.w ; edit_plot.D " 53 0 0 1
simundump xplot /graphs/conc2/Shc_EGFR.Co 3 524288 \
"delete_plot.w ; edit_plot.D " 58 0 0 1
simundump xplot /graphs/conc2/Grb_EGFR.Co 3 524288 \
"delete_plot.w ; edit_plot.D " 23 0 0 1
simundump xgraph /moregraphs/conc3 0 0 106 0 29.433 0
simundump xgraph /moregraphs/conc4 0 0 119 0 13.695 0
simundump xplot /moregraphs/conc3/SOS_EGFR.Co 3 524288 \
"delete_plot.w ; edit_plot.D " blue 0 0 1
simundump xplot /moregraphs/conc3/Sh-G-S.Co 3 524288 \
"delete_plot.w ; edit_plot.D " 52 0 0 1
simundump xplot /moregraphs/conc4/pPLCr.Co 3 524288 \
"delete_plot.w ; edit_plot.D " blue 0 0 1
simundump xcoredraw /edit/draw 0 -20 22 -53 -6
simundump xtree /edit/draw/tree 0 \
/kinetics/#[],/kinetics/#[]/#[],/kinetics/#[]/#[]/#[][TYPE!=proto],/kinetics/#[]/#[]/#[][TYPE!=linkinfo]/##[] \
"edit_elm.D ; drag_from_edit.w " auto 0.6
simundump xtext /file/notes 0 1
xtextload /file/notes \
"This model is based on the model and parameters published in paper:" \
"Quantificaion of Short Term Signaling by the EGFR;" \
"Kholodenko et al, The Journal of Biological Chemistry Vol 274, No. 42, Issue of October 15, pp. " \
"30169 - 30181, 1999." \
"Note: There are ambiguties in the paper about initial conditions employed for obtaining the results." \
"Thanks to Dr. Kholodenko for clarifying those ambiguties and passing on the actual values used." \
" [G-S]=33.04579, [Grb]=51.95431, [SOS]=0.95421."
addmsg /kinetics/r3 /kinetics/RP REAC B A
addmsg /kinetics/enz4/r4 /kinetics/RP REAC sA B
addmsg /kinetics/r5 /kinetics/RP REAC A B
addmsg /kinetics/r7 /kinetics/RP REAC B A
addmsg /kinetics/r13 /kinetics/RP REAC A B
addmsg /kinetics/r15 /kinetics/RP REAC B A
addmsg /kinetics/r18 /kinetics/RP REAC B A
addmsg /kinetics/r20 /kinetics/RP REAC B A
addmsg /kinetics/r9 /kinetics/RP REAC A B
addmsg /kinetics/r11 /kinetics/RP REAC B A
addmsg /kinetics/r2 /kinetics/R2 REAC B A
addmsg /kinetics/r3 /kinetics/R2 REAC A B
addmsg /kinetics/enz4/r4 /kinetics/R2 MM_PRD pA
addmsg /kinetics/enz4 /kinetics/enz4/r4 ENZYME n
addmsg /kinetics/RP /kinetics/enz4/r4 SUBSTRATE n
addmsg /kinetics/R2 /kinetics/r3 SUBSTRATE n
addmsg /kinetics/RP /kinetics/r3 PRODUCT n
addmsg /kinetics/Ra /kinetics/r2 SUBSTRATE n
addmsg /kinetics/R2 /kinetics/r2 PRODUCT n
addmsg /kinetics/Ra /kinetics/r2 SUBSTRATE n
addmsg /kinetics/r1 /kinetics/Ra REAC B A
addmsg /kinetics/r2 /kinetics/Ra REAC A B
addmsg /kinetics/r2 /kinetics/Ra REAC A B
addmsg /kinetics/r1 /kinetics/R REAC A B
addmsg /kinetics/r1 /kinetics/EGF REAC A B
addmsg /kinetics/EGF /kinetics/r1 SUBSTRATE n
addmsg /kinetics/Ra /kinetics/r1 PRODUCT n
addmsg /kinetics/R /kinetics/r1 SUBSTRATE n
addmsg /kinetics/r5 /kinetics/R-PL REAC B A
addmsg /kinetics/r6 /kinetics/R-PL REAC A B
addmsg /kinetics/r6 /kinetics/R-PLP REAC B A
addmsg /kinetics/r7 /kinetics/R-PLP REAC A B
addmsg /kinetics/r7 /kinetics/PLCrP REAC B A
addmsg /kinetics/r25 /kinetics/PLCrP REAC A B
addmsg /kinetics/enz8/r8 /kinetics/PLCrP REAC sA B
addmsg /kinetics/r5 /kinetics/PLCr REAC A B
addmsg /kinetics/enz8/r8 /kinetics/PLCr MM_PRD pA
addmsg /kinetics/RP /kinetics/r5 SUBSTRATE n
addmsg /kinetics/R-PL /kinetics/r5 PRODUCT n
addmsg /kinetics/PLCr /kinetics/r5 SUBSTRATE n
addmsg /kinetics/R-PL /kinetics/r6 SUBSTRATE n
addmsg /kinetics/R-PLP /kinetics/r6 PRODUCT n
addmsg /kinetics/R-PLP /kinetics/r7 SUBSTRATE n
addmsg /kinetics/PLCrP /kinetics/r7 PRODUCT n
addmsg /kinetics/RP /kinetics/r7 PRODUCT n
addmsg /kinetics/PLCrP /kinetics/r25 SUBSTRATE n
addmsg /kinetics/PLCr-I /kinetics/r25 PRODUCT n
addmsg /kinetics/r25 /kinetics/PLCr-I REAC B A
addmsg /kinetics/RP /kinetics/r13 SUBSTRATE n
addmsg /kinetics/R-Sh /kinetics/r13 PRODUCT n
addmsg /kinetics/Shc /kinetics/r13 SUBSTRATE n
addmsg /kinetics/r13 /kinetics/Shc REAC A B
addmsg /kinetics/enz16/r16 /kinetics/Shc MM_PRD pA
addmsg /kinetics/r14 /kinetics/R-Sh REAC A B
addmsg /kinetics/r13 /kinetics/R-Sh REAC B A
addmsg /kinetics/R-Sh /kinetics/r14 SUBSTRATE n
addmsg /kinetics/R-ShP /kinetics/r14 PRODUCT n
addmsg /kinetics/r15 /kinetics/R-ShP REAC A B
addmsg /kinetics/r17 /kinetics/R-ShP REAC A B
addmsg /kinetics/r24 /kinetics/R-ShP REAC A B
addmsg /kinetics/r14 /kinetics/R-ShP REAC B A
addmsg /kinetics/R-ShP /kinetics/r15 SUBSTRATE n
addmsg /kinetics/ShP /kinetics/r15 PRODUCT n
addmsg /kinetics/RP /kinetics/r15 PRODUCT n
addmsg /kinetics/r15 /kinetics/ShP REAC B A
addmsg /kinetics/r21 /kinetics/ShP REAC A B
addmsg /kinetics/r23 /kinetics/ShP REAC B A
addmsg /kinetics/enz16/r16 /kinetics/ShP REAC sA B
addmsg /kinetics/R-ShP /kinetics/r17 SUBSTRATE n
addmsg /kinetics/R-Sh-G /kinetics/r17 PRODUCT n
addmsg /kinetics/Grb /kinetics/r17 SUBSTRATE n
addmsg /kinetics/r17 /kinetics/R-Sh-G REAC B A
addmsg /kinetics/r18 /kinetics/R-Sh-G REAC A B
addmsg /kinetics/r19 /kinetics/R-Sh-G REAC A B
addmsg /kinetics/R-Sh-G /kinetics/r19 SUBSTRATE n
addmsg /kinetics/R-Sh-G-S /kinetics/r19 PRODUCT n
addmsg /kinetics/SOS /kinetics/r19 SUBSTRATE n
addmsg /kinetics/r19 /kinetics/R-Sh-G-S REAC B A
addmsg /kinetics/r20 /kinetics/R-Sh-G-S REAC A B
addmsg /kinetics/r24 /kinetics/R-Sh-G-S REAC B A
addmsg /kinetics/R-ShP /kinetics/r24 SUBSTRATE n
addmsg /kinetics/R-Sh-G-S /kinetics/r24 PRODUCT n
addmsg /kinetics/G-S /kinetics/r24 SUBSTRATE n
addmsg /kinetics/R-Sh-G /kinetics/r18 SUBSTRATE n
addmsg /kinetics/Sh-G /kinetics/r18 PRODUCT n
addmsg /kinetics/RP /kinetics/r18 PRODUCT n
addmsg /kinetics/R-Sh-G-S /kinetics/r20 SUBSTRATE n
addmsg /kinetics/Sh-G-S /kinetics/r20 PRODUCT n
addmsg /kinetics/RP /kinetics/r20 PRODUCT n
addmsg /kinetics/r22 /kinetics/Sh-G-S REAC B A
addmsg /kinetics/r20 /kinetics/Sh-G-S REAC B A
addmsg /kinetics/r23 /kinetics/Sh-G-S REAC A B
addmsg /kinetics/Sh-G /kinetics/r22 SUBSTRATE n
addmsg /kinetics/Sh-G-S /kinetics/r22 PRODUCT n
addmsg /kinetics/SOS /kinetics/r22 SUBSTRATE n
addmsg /kinetics/r21 /kinetics/Sh-G REAC B A
addmsg /kinetics/r18 /kinetics/Sh-G REAC B A
addmsg /kinetics/r22 /kinetics/Sh-G REAC A B
addmsg /kinetics/ShP /kinetics/r21 SUBSTRATE n
addmsg /kinetics/Sh-G /kinetics/r21 PRODUCT n
addmsg /kinetics/Grb /kinetics/r21 SUBSTRATE n
addmsg /kinetics/Sh-G-S /kinetics/r23 SUBSTRATE n
addmsg /kinetics/G-S /kinetics/r23 PRODUCT n
addmsg /kinetics/ShP /kinetics/r23 PRODUCT n
addmsg /kinetics/r23 /kinetics/G-S REAC B A
addmsg /kinetics/r11 /kinetics/G-S REAC B A
addmsg /kinetics/r24 /kinetics/G-S REAC A B
addmsg /kinetics/r12 /kinetics/G-S REAC A B
addmsg /kinetics/R-G-S /kinetics/r11 SUBSTRATE n
addmsg /kinetics/G-S /kinetics/r11 PRODUCT n
addmsg /kinetics/RP /kinetics/r11 PRODUCT n
addmsg /kinetics/r17 /kinetics/Grb REAC A B
addmsg /kinetics/r21 /kinetics/Grb REAC A B
addmsg /kinetics/r9 /kinetics/Grb REAC A B
addmsg /kinetics/r12 /kinetics/Grb REAC B A
addmsg /kinetics/RP /kinetics/r9 SUBSTRATE n
addmsg /kinetics/Grb /kinetics/r9 SUBSTRATE n
addmsg /kinetics/R-G /kinetics/r9 PRODUCT n
addmsg /kinetics/G-S /kinetics/r12 SUBSTRATE n
addmsg /kinetics/Grb /kinetics/r12 PRODUCT n
addmsg /kinetics/SOS /kinetics/r12 PRODUCT n
addmsg /kinetics/r9 /kinetics/R-G REAC B A
addmsg /kinetics/r10 /kinetics/R-G REAC A B
addmsg /kinetics/R-G /kinetics/r10 SUBSTRATE n
addmsg /kinetics/R-G-S /kinetics/r10 PRODUCT n
addmsg /kinetics/SOS /kinetics/r10 SUBSTRATE n
addmsg /kinetics/r12 /kinetics/SOS REAC B A
addmsg /kinetics/r10 /kinetics/SOS REAC A B
addmsg /kinetics/r22 /kinetics/SOS REAC A B
addmsg /kinetics/r19 /kinetics/SOS REAC A B
addmsg /kinetics/r11 /kinetics/R-G-S REAC A B
addmsg /kinetics/r10 /kinetics/R-G-S REAC B A
addmsg /kinetics/enz8 /kinetics/enz8/r8 ENZYME n
addmsg /kinetics/PLCrP /kinetics/enz8/r8 SUBSTRATE n
addmsg /kinetics/enz16 /kinetics/enz16/r16 ENZYME n
addmsg /kinetics/ShP /kinetics/enz16/r16 SUBSTRATE n
addmsg /kinetics/RP /kinetics/pEGFRtot SUMTOTAL n nInit
addmsg /kinetics/R-PL /kinetics/pEGFRtot SUMTOTAL n nInit
addmsg /kinetics/R-PLP /kinetics/pEGFRtot SUMTOTAL n nInit
addmsg /kinetics/R-G /kinetics/pEGFRtot SUMTOTAL n nInit
addmsg /kinetics/R-G-S /kinetics/pEGFRtot SUMTOTAL n nInit
addmsg /kinetics/R-Sh /kinetics/pEGFRtot SUMTOTAL n nInit
addmsg /kinetics/R-ShP /kinetics/pEGFRtot SUMTOTAL n nInit
addmsg /kinetics/R-Sh-G /kinetics/pEGFRtot SUMTOTAL n nInit
addmsg /kinetics/R-Sh-G-S /kinetics/pEGFRtot SUMTOTAL n nInit
addmsg /kinetics/R-ShP /kinetics/pShctot SUMTOTAL n nInit
addmsg /kinetics/R-Sh-G /kinetics/pShctot SUMTOTAL n nInit
addmsg /kinetics/R-Sh-G-S /kinetics/pShctot SUMTOTAL n nInit
addmsg /kinetics/ShP /kinetics/pShctot SUMTOTAL n nInit
addmsg /kinetics/Sh-G /kinetics/pShctot SUMTOTAL n nInit
addmsg /kinetics/Sh-G-S /kinetics/pShctot SUMTOTAL n nInit
addmsg /kinetics/R-Sh-G /kinetics/Grb2_Shc SUMTOTAL n nInit
addmsg /kinetics/Sh-G /kinetics/Grb2_Shc SUMTOTAL n nInit
addmsg /kinetics/R-Sh-G-S /kinetics/Grb2_Shc SUMTOTAL n nInit
addmsg /kinetics/Sh-G-S /kinetics/Grb2_Shc SUMTOTAL n nInit
addmsg /kinetics/R-ShP /kinetics/Shc_EGFR SUMTOTAL n nInit
addmsg /kinetics/R-Sh-G /kinetics/Shc_EGFR SUMTOTAL n nInit
addmsg /kinetics/R-Sh-G-S /kinetics/Shc_EGFR SUMTOTAL n nInit
addmsg /kinetics/R-G /kinetics/Grb_EGFR SUMTOTAL n nInit
addmsg /kinetics/R-G-S /kinetics/Grb_EGFR SUMTOTAL n nInit
addmsg /kinetics/R-Sh-G /kinetics/Grb_EGFR SUMTOTAL n nInit
addmsg /kinetics/R-Sh-G-S /kinetics/Grb_EGFR SUMTOTAL n nInit
addmsg /kinetics/R-G-S /kinetics/SOS_EGFR SUMTOTAL n nInit
addmsg /kinetics/R-Sh-G-S /kinetics/SOS_EGFR SUMTOTAL n nInit
addmsg /kinetics/R-PLP /kinetics/pPLCr SUMTOTAL n nInit
addmsg /kinetics/PLCrP /kinetics/pPLCr SUMTOTAL n nInit
addmsg /kinetics/pEGFRtot /graphs/conc1/pEGFRtot.Co PLOT Co *pEGFRtot.Co *2
addmsg /kinetics/pShctot /graphs/conc1/pShctot.Co PLOT Co *pShctot.Co *blue
addmsg /kinetics/Grb2_Shc /graphs/conc1/Grb2_Shc.Co PLOT Co *Grb2_Shc.Co *53
addmsg /kinetics/Shc_EGFR /graphs/conc2/Shc_EGFR.Co PLOT Co *Shc_EGFR.Co *58
addmsg /kinetics/Grb_EGFR /graphs/conc2/Grb_EGFR.Co PLOT Co *Grb_EGFR.Co *23
addmsg /kinetics/SOS_EGFR /moregraphs/conc3/SOS_EGFR.Co PLOT Co *SOS_EGFR.Co *blue
addmsg /kinetics/Sh-G-S /moregraphs/conc3/Sh-G-S.Co PLOT Co *Sh-G-S.Co *52
addmsg /kinetics/pPLCr /moregraphs/conc4/pPLCr.Co PLOT Co *pPLCr.Co *blue
enddump
// End of dump
call /kinetics/RP/notes LOAD \
" Taken from Kholodenko et al 1999."
call /kinetics/R2/notes LOAD \
"Taken form Kholodenko et al 1999."
call /kinetics/enz4/notes LOAD \
" The initial conentration was set to 1nM"
call /kinetics/enz4/r4/notes LOAD \
" Taken from Kholodenko et al 1999."
call /kinetics/r3/notes LOAD \
"Taken from Kholodenko et al 1999."
call /kinetics/r2/notes LOAD \
" Taken from Kholodenko et al 1999"
call /kinetics/Ra/notes LOAD \
" Taken form Kholodenko et al 1999" \
""
call /kinetics/R/notes LOAD \
"Taken form Kholodenko et al 1999." \
"[EGFR] = 100nM." \
"To obtain the plots as per figure-7B [EGFR] was increased " \
"4-fold (400nM) to obtain plot-1 and " \
"decreased 4-fold (25nM) to obtain plot-2." \
""
call /kinetics/EGF/notes LOAD \
"Taken from Kholodenko et al 1999" \
"Simulations were done at EGF concentration set to 20nM and 2nM" \
"concentration. This concentration was multiplied by a constant " \
"factor Vm/Vcw = 33.3 to formally rescale it to the cytoplasmic" \
"water volume. So actual concentration to which EGF was set was" \
"666nM and 66.6nM." \
"Plots 1&3 of figure-5 and plot 1 of figure 4 are obtained" \
"by setting the EGF conc to 666nM." \
"Plots 2&4 of figure-5 and plot 3 of figure 4 are obtained " \
"by setting the EGF conc to 66.6nM." \
"" \
""
call /kinetics/r1/notes LOAD \
"Taken from Kholodenko et al 1999." \
""
call /kinetics/R-PL/notes LOAD \
"Taken from Kholodenko et al 1999. "
call /kinetics/R-PLP/notes LOAD \
"Taken from Kholodenko et al 1999. "
call /kinetics/PLCrP/notes LOAD \
"Taken from Kholodenko et al 1999. "
call /kinetics/PLCr/notes LOAD \
"Taken from Kholodenko et al 1999. PLC-gamma"
call /kinetics/r5/notes LOAD \
"Taken from Kholodenko et al 1999. "
call /kinetics/r6/notes LOAD \
"Taken from Kholodenko et al 1999. "
call /kinetics/r7/notes LOAD \
"Taken from Kholodenko et al 1999. "
call /kinetics/r25/notes LOAD \
"Taken from Kholodenko et al 1999. "
call /kinetics/PLCr-I/notes LOAD \
"Taken from Kholodenko et al 1999. "
call /kinetics/r13/notes LOAD \
"Taken from Kholodenko et al 1999."
call /kinetics/Shc/notes LOAD \
"Taken from Kholodenko et al 1999." \
"To get plots in figure-4 and figure-5 [Shc] is set to 150nM" \
"To get plots in figure-7A [Shc] is set to 37.5nM" \
"(4-fold decrease)." \
""
call /kinetics/R-Sh/notes LOAD \
"Taken from Kholodenko et al 1999."
call /kinetics/r14/notes LOAD \
"Taken from Kholodenko et al 1999."
call /kinetics/R-ShP/notes LOAD \
"Taken from Kholodenko et al 1999."
call /kinetics/r15/notes LOAD \
"Taken from Kholodenko et al 1999."
call /kinetics/ShP/notes LOAD \
"Taken from Kholodenko et al 1999."
call /kinetics/r17/notes LOAD \
"Taken from Kholodenko et al 1999."
call /kinetics/R-Sh-G/notes LOAD \
"Taken from Kholodenko et al 1999."
call /kinetics/r19/notes LOAD \
"Taken from Kholodenko et al 1999." \
""
call /kinetics/R-Sh-G-S/notes LOAD \
"Taken from Kholodenko et al 1999."
call /kinetics/r24/notes LOAD \
"Taken from Kholodenko et al 1999."
call /kinetics/r18/notes LOAD \
"Taken from Kholodenko et al 1999."
call /kinetics/r20/notes LOAD \
"Taken from Kholodenko et al 1999."
call /kinetics/Sh-G-S/notes LOAD \
"Taken from Kholodenko et al 1999." \
"Phosphorylated Shc [Sh-G-S]"
call /kinetics/r22/notes LOAD \
"Taken from Kholodenko et al 1999."
call /kinetics/Sh-G/notes LOAD \
"Taken from Kholodenko et al 1999."
call /kinetics/r21/notes LOAD \
"Taken from Kholodenko et al 1999."
call /kinetics/r23/notes LOAD \
"Taken form Kholodenko et al 1999"
call /kinetics/G-S/notes LOAD \
"" \
"Thanks to Dr. Kholodenko for clarifying the ambiguity " \
"and furnishing the values." \
""
call /kinetics/r11/notes LOAD \
"Taken from Kholodenko et al 1999."
call /kinetics/Grb/notes LOAD \
"Taken from Kholodenko et al 1999." \
"To obtain plots as per figure-4 and 5 [Grb] is set to 51.954nM." \
"instead of 85nM. Thanks to Dr. Kholodenko for clarifying the" \
"ambiguity and furnishing us the above value." \
"" \
" To obtain plots as per figure-7A [Grb] is set to 340nM " \
"(4-fold increase)."
call /kinetics/r9/notes LOAD \
"Taken from Kholodenko et al 1999."
call /kinetics/r12/notes LOAD \
"Taken from Kholodenko et al 1999."
call /kinetics/R-G/notes LOAD \
"Taken from Kholodenko et al 1999" \
""
call /kinetics/r10/notes LOAD \
"Taken from Kholodenko et al 1999"
call /kinetics/SOS/notes LOAD \
"The initial concentration is set to 0.95421nM instead of 37nM which." \
"Thanks to Dr. Kholodenko for clarifying the ambiguity and " \
"furnishing the initial concentration."
call /kinetics/R-G-S/notes LOAD \
"Taken from Kholodenko et al 1999."
call /kinetics/enz8/notes LOAD \
"The initial concentration was set ot 1nM."
call /kinetics/enz8/r8/notes LOAD \
"Taken from Kholodenko et al 1999. "
call /kinetics/enz16/notes LOAD \
"Taken from Kholodenko et al 1999."
call /kinetics/enz16/r16/notes LOAD \
"Taken from Kholodenko et al 1999."
call /kinetics/pEGFRtot/notes LOAD \
"Taken from Kholodenko et al 1999." \
"Total phosphorylated EGFR = 2.([RP] + [R-PL] + [R-PLP] + [R-G]" \
"+ [R-G-S] + [R-Sh] + [R-ShP] + [R-Sh-G] + [R-Sh-G-S] )"
call /kinetics/pShctot/notes LOAD \
"Taken from Kholodenko et al 1999." \
"Total phosphorylated Shc = [ShP] + [Sh-G] + [ Sh-G-S] + [R-ShP]" \
"[R-Sh-G] + [R-Sh-G-S]"
call /kinetics/Grb2_Shc/notes LOAD \
"Taken from Kholodenko et al 1999." \
"Total Concentration of Grb2 bound to Shc isoforms= [Sh-G-S]" \
"[R-Sh-G] +[R-Sh-G-S] + [Sh-G]" \
""
call /kinetics/Shc_EGFR/notes LOAD \
"Taken from Kholodenko et al 1999." \
"Shc bound to EGFR = [R-ShP] + [ R-Sh-G] + [R-Sh-G-S]"
call /kinetics/Grb_EGFR/notes LOAD \
"Taken from Kholodenko et al 1999." \
"Total concentration of Grb2 bound to EGFR forms =" \
"[R-G] + [R-G-S] + [R-Sh-G] + [R-Sh-G-S]" \
""
call /kinetics/SOS_EGFR/notes LOAD \
"Taken from Kholodenko et al 1999." \
"Total Sos bound to EGFR = [R-G-S] + [R-Sh-G-S]" \
""
call /kinetics/pPLCr/notes LOAD \
"According to Kholodenko et al 1999." \
"" \
"Total Phosphorylated PLCr = [R-PLP] + [PLCrP]." \
""
call /kinetics/doqcsinfo/notes LOAD \
" This model is based on the model and parameters published in paper: Quantification of Short Term Signaling by the EGFR Kholodenko et al, The J Biol Chem. , Vol 274, No. 42, Issue of October 15, pp. 30169 - 30181, 1999.
Note: There are a few small ambiguities in the paper about initial conditions employed for obtaining the results. Thanks to Dr. Kholodenko for clarifying those ambiguities and providing the values used in the simulations:[G-S]=33.04579, [Grb]=51.95431, [SOS]=0.95421."
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