//genesis
// kkit Version 11 flat dumpfile
// Saved on Fri Oct 10 15:43:56 2008
include kkit {argv 1}
FASTDT = 2e-06
SIMDT = 0.001
CONTROLDT = 1
PLOTDT = 10
MAXTIME = 6000
TRANSIENT_TIME = 2
VARIABLE_DT_FLAG = 1
DEFAULT_VOL = 1e-15
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
simobjdump text str
simundump geometry /kinetics/geometry 0 1e-15 3 sphere "" white black 0 0 0
simundump geometry /kinetics/geometry[1] 0 1e-15 3 sphere "" white black 11 \
20 0
simundump geometry /kinetics/geometry[2] 0 1e-15 3 sphere "" white black 6 20 \
0
simundump geometry /kinetics/geometry[3] 0 1e-15 3 sphere "" white black 5 20 \
0
simundump geometry /kinetics/geometry[4] 0 1e-15 3 sphere "" white black 7 20 \
0
simundump geometry /kinetics/geometry[5] 0 1e-15 3 sphere "" white black 9 20 \
0
simundump geometry /kinetics/geometry[6] 0 1e-15 3 sphere "" white black 10 \
20 0
simundump geometry /kinetics/geometry[7] 0 1e-15 3 sphere "" white black 8 20 \
0
simundump geometry /kinetics/geometry[8] 0 1e-15 3 sphere "" white black 0 0 \
0
simundump geometry /kinetics/geometry[9] 0 1e-15 3 sphere "" white black 0 0 \
0
simundump geometry /kinetics/geometry[10] 0 1e-15 3 sphere "" white black 0 0 \
0
simundump geometry /kinetics/geometry[11] 0 1e-15 3 sphere "" white black 0 0 \
0
simundump geometry /kinetics/geometry[12] 0 1e-15 3 sphere "" white black 0 0 \
0
simundump geometry /kinetics/geometry[13] 0 1e-15 3 sphere "" white black 0 0 \
0
simundump geometry /kinetics/geometry[14] 0 1e-15 3 sphere "" white black 0 0 \
0
simundump geometry /kinetics/geometry[15] 0 1e-15 3 sphere "" white black 0 0 \
0
simundump geometry /kinetics/geometry[16] 0 1e-15 3 sphere "" white black 0 0 \
0
simundump kpool /kinetics/BDNF 0 0 5e-05 5e-05 29.999 29.999 0 0 5.9998e+05 4 \
/kinetics/geometry 44 black -14 16 0
simundump kpool /kinetics/PLC_g 0 0 0.1 0.1 60000 60000 0 0 6e+05 0 \
/kinetics/geometry cyan black -3 7 0
simundump kpool /kinetics/PLC_g_star 0 0 0 0 0 0 0 0 6e+05 0 \
/kinetics/geometry "hot pink" black -1 7 0
simundump kpool /kinetics/PIP3 0 0 0 0 0 0 0 0 5.9998e+05 0 \
/kinetics/geometry 43 black -3 -11 0
simundump kpool /kinetics/PDK1 0 0 1 1 6e+05 6e+05 0 0 6e+05 0 \
/kinetics/geometry[2] 37 black 3 6 0
simundump kenz /kinetics/PDK1/S6K_phospho 0 0 0 0 0 6e+05 8.3333e-07 4 1 0 0 \
"" red 37 "" 7 -7 0
simundump kpool /kinetics/PP2A 0 0 0.15 0.15 90000 90000 0 0 6e+05 0 \
/kinetics/geometry 4 black 11 1 0
simundump kenz /kinetics/PP2A/dephos_clus_S6K 0 0 0 0 0 5.9998e+05 9.4696e-07 \
4 1 0 0 "" red 25 "" 3 1 0
simundump kenz /kinetics/PP2A/dephos_S6K 0 0 0 0 0 5.9998e+05 9.4696e-07 4 1 \
0 0 "" red 25 "" 9 -2 0
simundump kenz /kinetics/PP2A/dephosp_S6K 0 0 0 0 0 5.9998e+05 9.4696e-07 4 1 \
0 0 "" red 25 "" 13 -2 0
simundump kenz /kinetics/PP2A/Dephos_AKTser473 0 0 0 0 0 6e+05 3.125e-06 7.2 \
1.8 0 0 "" red 46 "" 3 -8 0
simundump kenz /kinetics/PP2A/Dephosph_AKTthr308 0 0 0 0 0 6e+05 3.1249e-06 \
7.2 1.8 0 0 "" red 46 "" 0 -8 0
simundump kenz /kinetics/PP2A/eEF2thr-56_dephospho 0 0 0 0 0 6e+05 4.4506e-07 \
1.88 0.47 0 0 "" red 4 "" 23 8 0
simundump kenz /kinetics/PP2A/PP2A_4E-BP_star_star 0 0 0 0 0 6e+05 9.4697e-07 \
4 1 0 0 "" red 4 "" -11 -10 0
simundump kenz /kinetics/PP2A/PP2A_4E-BP_star 0 0 0 0 0 6e+05 9.4697e-07 4 1 \
0 0 "" red 4 "" -9 -17 0
simundump kenz /kinetics/PP2A/PP2A_4E-BP 0 0 0 0 0 6e+05 9.4694e-07 4 1 0 0 \
"" red 62 "" -13 -3 0
simundump kenz /kinetics/PP2A/PP2A_4EBP 0 0 0 0 0 6e+05 9.4694e-07 4 1 0 0 "" \
red 62 "" -13 -7 0
simundump group /kinetics/AKT_mod 0 yellow black x 0 0 "" AKT_mod \
defaultfile.g 0 0 0 5 8 0
simundump kpool /kinetics/AKT_mod/PIP3_AKT 0 0 0 0 0 0 0 0 5.9998e+05 0 \
/kinetics/geometry 53 yellow -8 4 0
simundump kpool /kinetics/AKT_mod/PIP3_PDK1 0 0 0 0 0 0 0 0 6e+05 0 \
/kinetics/geometry 9 yellow -4 10 0
simundump kenz /kinetics/AKT_mod/PIP3_PDK1/phospho_thr308 0 0 0 0 0 2999.9 \
0.00020834 40 10 0 0 "" red 9 "" -4 8 0
simundump kpool /kinetics/AKT_mod/PIP3_PDK2 0 0 0.003 0.003 1800 1800 0 0 \
6e+05 0 /kinetics/geometry 39 yellow 2 10 0
simundump kenz /kinetics/AKT_mod/PIP3_PDK2/phosp_AKTser473 0 0 0 0 0 6e+05 \
0.00020833 80 20 0 0 "" red 39 "" 2 13 0
simundump kpool /kinetics/AKT_mod/PIP3_AKT_thr308 0 0 0 0 0 0 0 0 5.9998e+05 \
0 /kinetics/geometry 60 yellow -4 4 0
simundump kpool /kinetics/AKT_mod/PIP3_AKT-t308_s473 0 0 0 0 0 0 0 0 6e+05 0 \
/kinetics/geometry 25 yellow 4 11 0
simundump kenz /kinetics/AKT_mod/PIP3_AKT-t308_s473/TSC2_phospho 0 0 0 0 0 \
6e+05 4.8544e-06 24 6 0 0 "" red 25 "" 8 11 0
simundump kpool /kinetics/AKT_mod/AKT 0 0 0.20001 0.20001 1.2e+05 1.2e+05 0 0 \
5.9998e+05 0 /kinetics/geometry 4 yellow -11 1 0
simundump kpool /kinetics/AKT_mod/TSC1-TSC2_star 0 0 0 0 0 0 0 0 6e+05 0 \
/kinetics/geometry 40 yellow 5 2 0
simundump kreac /kinetics/AKT_mod/PIP3_bind_AKT 0 7.5003e-05 0.089 "" white \
yellow -11 4 0
simundump kreac /kinetics/AKT_mod/PIP3_bind_PDK1 0 1.1667e-06 0.98 "" white \
yellow -8 6 0
simundump kreac /kinetics/AKT_mod/TSC1-2_dephospho 0 0.01 0 "" white yellow \
10 7 0
simundump group /kinetics/TrKB_mod 0 white black x 0 0 "" TrKB_mod \
defaultfile.g 0 0 0 1 8 0
simundump kpool /kinetics/TrKB_mod/Int_BDNF_TrKB2_star_clx 0 0 0.25 0.25 \
1.5e+05 1.5e+05 0 0 6e+05 4 /kinetics/geometry yellow white -9 12 0
simundump kpool /kinetics/TrKB_mod/TrKB 0 0 0.25 0.25 1.4999e+05 1.4999e+05 0 \
0 5.9996e+05 0 /kinetics/geometry 3 white -7 3 0
simundump kpool /kinetics/TrKB_mod/BDNF_TrkB2_clx 0 0 0 0 0 0 0 0 5.9998e+05 \
0 /kinetics/geometry 38 white -5 3 0
simundump kreac /kinetics/TrKB_mod/Autophos_TrKB 0 0.02 0 "" white white -4 \
-2 0
simundump kreac /kinetics/TrKB_mod/Dimeriz_TrKB 0 1.6667e-06 0.02 "" white \
white -7 0 0
simundump kpool /kinetics/TrKB_mod/BDNF_TrkB_clx 0 0 0 0 0 0 0 0 5.9996e+05 0 \
/kinetics/geometry 45 white -6 -3 0
simundump kreac /kinetics/TrKB_mod/Ligand_binding 0 1.6668e-06 0.05 "" white \
white -9 0 0
simundump kpool /kinetics/TrKB_mod/BDNF_TrkB2_star_clx 0 0 0 0 0 0 0 0 \
5.9998e+05 0 /kinetics/geometry red white -3 3 0
simundump kenz /kinetics/TrKB_mod/BDNF_TrkB2_star_clx/PLC_g_phospho 0 0 0 0 0 \
5.9998e+05 1.3889e-05 2 0.5 0 0 "" red red "" -3 5 0
simundump kenz /kinetics/TrKB_mod/BDNF_TrkB2_star_clx/Shc_phospho 0 0 0 0 0 \
5.9998e+05 3.0002e-06 1.2 0.3 0 0 "" red red "" -3 2 0
simundump kreac /kinetics/TrKB_mod/PLC_g_star_dephospho 0 0.07 0 "" white \
white -1 12 0
simundump kpool /kinetics/TrKB_mod/Shc_star_Grb2-Gab1_PI3K_clx 0 0 0 0 0 0 0 \
0 5.9998e+05 0 /kinetics/geometry brown white 2 -3 0
simundump kenz /kinetics/TrKB_mod/Shc_star_Grb2-Gab1_PI3K_clx/Phospho 0 0 0 0 \
0 5.9998e+05 8.3336e-06 16 4 0 0 "" red brown "" 2 -4 0
simundump kreac /kinetics/TrKB_mod/LR_Internalize 0 0.01 0 "" white white -5 \
9 0
simundump kreac /kinetics/TrKB_mod/LR_cycling 0 0.001 0.001 "" white white -9 \
9 0
simundump group /kinetics/PI3K_mod 0 brown black x 0 0 "" PI3K_mod \
defaultfile.g 0 0 0 -9 -15 0
simundump kpool /kinetics/PI3K_mod/PI3K 0 0 0.1 0.1 59998 59998 0 0 \
5.9998e+05 0 /kinetics/geometry cyan brown 4 -18 0
simundump kpool /kinetics/PI3K_mod/PI3K_basal 0 0 0 0 0 0 0 0 6e+05 0 \
/kinetics/geometry 10 brown -3 -17 0
simundump kenz /kinetics/PI3K_mod/PI3K_basal/basal_phosp 0 0 0 0 0 6e+05 \
8.3333e-06 16 4 0 0 "" red 10 "" -3 -16 0
simundump kpool /kinetics/PI3K_mod/PIP2 0 0 7 7 4.2e+06 4.2e+06 0 0 6e+05 4 \
/kinetics/geometry orange brown 1 -11 0
simundump kpool /kinetics/PI3K_mod/Shc 0 0 0.5 0.5 3e+05 3e+05 0 0 6e+05 0 \
/kinetics/geometry 5 brown -3 -6 0
simundump kreac /kinetics/PI3K_mod/Shc_star_dephospho 0 0.2 0 "" white brown \
-2 -9 0
simundump kreac /kinetics/PI3K_mod/Grb2_bind_Shc 0 1.6667e-06 1 "" white \
brown 0 -4 0
simundump kpool /kinetics/PI3K_mod/Shc_star_Grb2_clx 0 0 0 0 0 0 0 0 6e+05 0 \
/kinetics/geometry[2] 42 brown 2 -7 0
simundump kpool /kinetics/PI3K_mod/Gab1 0 0 0.7 0.7 4.2e+05 4.2e+05 0 0 6e+05 \
0 /kinetics/geometry[1] 44 brown 2 -5 0
simundump kreac /kinetics/PI3K_mod/bind_Gab1 0 5e-07 1 "" white brown 5 -5 0
simundump kpool /kinetics/PI3K_mod/Shc_star_Grb2-Gab1_clx 0 0 0 0 0 0 0 0 \
6e+05 0 /kinetics/geometry 50 brown 6 -9 0
simundump kreac /kinetics/PI3K_mod/PI3K_act 0 8.3336e-06 0.08 "" white brown \
4 -13 0
simundump kreac /kinetics/PI3K_mod/basal_PI3K_act 0 0.00068 0.45 "" white \
brown 1 -19 0
simundump kpool /kinetics/PLCg_basal 0 0 0.0007 0.0007 420 420 0 0 6e+05 0 \
/kinetics/geometry[4] 33 black -3 11 0
simundump kenz /kinetics/PLCg_basal/PLC_g_phospho 0 0 0 0 0 6e+05 1.3889e-05 \
2 0.5 0 0 "" red 33 "" -3 10 0
simundump kpool /kinetics/TSC1-TSC2 0 0 1 1 6e+05 6e+05 0 0 6e+05 0 \
/kinetics/geometry 51 black 12 9 0
simundump kenz /kinetics/TSC1-TSC2/TSC2phospho 0 0 0 0 0 6e+05 0.00055556 80 \
20 0 0 "" red 51 "" 12 8 0
simundump kpool /kinetics/eIF4E 0 0 0 0 0 0 0 0 5.9999e+05 0 \
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simundump kpool /kinetics/Rheb-GTP 0 0 1 1 6e+05 6e+05 0 0 6e+05 0 \
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simundump kpool /kinetics/Rheb-GDP 0 0 0 0 0 0 0 0 6e+05 0 \
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simundump group /kinetics/mTOR_model 0 8 black x 0 0 "" mTOR_model \
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simundump kreac /kinetics/mTOR_model/Rheb-GTP_bind_TORclx 0 1e-05 3 "" white \
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simundump kpool /kinetics/mTOR_model/TOR-clx 0 0 0.6 0.6 3.6e+05 3.6e+05 0 0 \
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simundump kpool /kinetics/TOR_Rheb-GTP_clx 0 0 0 0 0 0 0 0 6e+05 0 \
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simundump kenz /kinetics/TOR_Rheb-GTP_clx/S6K_phospho 0 0 0 0 0 6e+05 \
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simundump kenz /kinetics/TOR_Rheb-GTP_clx/TOR_4E-BP_phospho 0 0 0 0 0 6e+05 \
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simundump kenz /kinetics/TOR_Rheb-GTP_clx/TOR_4E-BP_star 0 0 0 0 0 6e+05 \
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simundump group /kinetics/S6Kinase 0 6 black x 0 0 "" defaultfile \
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simundump kpool /kinetics/S6Kinase/S6K_star 0 0 0 0 0 0 0 0 5.9998e+05 0 \
/kinetics/geometry 46 6 3 4 0
simundump kpool /kinetics/S6Kinase/S6K 0 0 1.25 1.25 7.5e+05 7.5e+05 0 0 \
6e+05 0 /kinetics/geometry Pink 6 0 3 0
simundump kpool /kinetics/S6Kinase/S6K_thr-412 0 0 0 0 0 0 0 0 5.9998e+05 0 \
/kinetics/geometry 48 6 7 -16 0
simundump kenz /kinetics/S6Kinase/S6K_thr-412/S6_phos 0 0 0 0 0 5.9998e+05 \
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simundump kreac /kinetics/S6Kinase/S6_dephosph 0 0.01 0 "" white 6 14 5 0
simundump kpool /kinetics/S6Kinase/40S_inact 0 0 0.02 0.02 12000 12000 0 0 \
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simundump group /kinetics/4E-BP_mod 0 white black x 0 0 "" 4E-BP_mod \
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simundump kreac /kinetics/4E-BP_mod/eIF4E_bind_BP2 0 8.3333e-05 0.15 "" white \
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simundump kreac /kinetics/4E-BP_mod/eIF4E-BP2_disso 0 4 1.6667e-06 "" white \
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simundump kpool /kinetics/4E-BP_mod/4E-BP 0 0 0 0 0 0 0 0 6e+05 0 \
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simundump kreac /kinetics/eIF4F_clx 0 5.0001e-05 0.1 "" white black -15 10 0
simundump kpool /kinetics/eIF4G-A_clx 0 0 0 0 0 0 0 0 5.9999e+05 0 \
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simundump kreac /kinetics/eIF4G_A_clx 0 5.0001e-07 1 "" white black -7 9 0
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addmsg /kinetics/TrKB_mod/Ligand_binding /kinetics/BDNF REAC A B
addmsg /kinetics/TrKB_mod/BDNF_TrkB2_star_clx/PLC_g_phospho /kinetics/PLC_g REAC sA B
addmsg /kinetics/TrKB_mod/PLC_g_star_dephospho /kinetics/PLC_g REAC B A
addmsg /kinetics/PLCg_basal/PLC_g_phospho /kinetics/PLC_g REAC sA B
addmsg /kinetics/TrKB_mod/BDNF_TrkB2_star_clx/PLC_g_phospho /kinetics/PLC_g_star MM_PRD pA
addmsg /kinetics/TrKB_mod/PLC_g_star_dephospho /kinetics/PLC_g_star REAC A B
addmsg /kinetics/PLCg_basal/PLC_g_phospho /kinetics/PLC_g_star MM_PRD pA
addmsg /kinetics/TrKB_mod/Shc_star_Grb2-Gab1_PI3K_clx/Phospho /kinetics/PIP3 MM_PRD pA
addmsg /kinetics/PI3K_mod/PI3K_basal/basal_phosp /kinetics/PIP3 MM_PRD pA
addmsg /kinetics/AKT_mod/PIP3_bind_PDK1 /kinetics/PIP3 REAC A B
addmsg /kinetics/AKT_mod/PIP3_bind_AKT /kinetics/PIP3 REAC A B
addmsg /kinetics/PTEN/PIP3_dephosp /kinetics/PIP3 REAC sA B
addmsg /kinetics/Ras-GTP_PI3K/PIP2_phospho_Ras-GTP /kinetics/PIP3 MM_PRD pA
addmsg /kinetics/AKT_mod/PIP3_bind_PDK1 /kinetics/PDK1 REAC A B
addmsg /kinetics/PDK1/S6K_phospho /kinetics/PDK1 REAC eA B
addmsg /kinetics/PDK1 /kinetics/PDK1/S6K_phospho ENZYME n
addmsg /kinetics/S6Kinase/S6K_thr-412 /kinetics/PDK1/S6K_phospho SUBSTRATE n
addmsg /kinetics/PP2A/Dephos_AKTser473 /kinetics/PP2A REAC eA B
addmsg /kinetics/PP2A/Dephosph_AKTthr308 /kinetics/PP2A REAC eA B
addmsg /kinetics/PP2A/dephos_S6K /kinetics/PP2A REAC eA B
addmsg /kinetics/PP2A/dephos_clus_S6K /kinetics/PP2A REAC eA B
addmsg /kinetics/PP2A/dephosp_S6K /kinetics/PP2A REAC eA B
addmsg /kinetics/PP2A/PP2A_4EBP /kinetics/PP2A REAC eA B
addmsg /kinetics/PP2A/PP2A_4E-BP /kinetics/PP2A REAC eA B
addmsg /kinetics/PP2A/eEF2thr-56_dephospho /kinetics/PP2A REAC eA B
addmsg /kinetics/PP2A/PP2A_4E-BP_star_star /kinetics/PP2A REAC eA B
addmsg /kinetics/PP2A/PP2A_4E-BP_star /kinetics/PP2A REAC eA B
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addmsg /kinetics/S6Kinase/S6K_star /kinetics/PP2A/dephos_clus_S6K SUBSTRATE n
addmsg /kinetics/PP2A /kinetics/PP2A/dephos_S6K ENZYME n
addmsg /kinetics/S6Kinase/S6K_thr-412 /kinetics/PP2A/dephos_S6K SUBSTRATE n
addmsg /kinetics/PP2A /kinetics/PP2A/dephosp_S6K ENZYME n
addmsg /kinetics/S6K_thr-252 /kinetics/PP2A/dephosp_S6K SUBSTRATE n
addmsg /kinetics/PP2A /kinetics/PP2A/Dephos_AKTser473 ENZYME n
addmsg /kinetics/AKT_mod/PIP3_AKT-t308_s473 /kinetics/PP2A/Dephos_AKTser473 SUBSTRATE n
addmsg /kinetics/PP2A /kinetics/PP2A/Dephosph_AKTthr308 ENZYME n
addmsg /kinetics/AKT_mod/PIP3_AKT_thr308 /kinetics/PP2A/Dephosph_AKTthr308 SUBSTRATE n
addmsg /kinetics/PP2A /kinetics/PP2A/eEF2thr-56_dephospho ENZYME n
addmsg /kinetics/eEFthr-56 /kinetics/PP2A/eEF2thr-56_dephospho SUBSTRATE n
addmsg /kinetics/PP2A /kinetics/PP2A/PP2A_4E-BP_star_star ENZYME n
addmsg /kinetics/4E-BP_mod/4E-BP_thr37_46_s65 /kinetics/PP2A/PP2A_4E-BP_star_star SUBSTRATE n
addmsg /kinetics/PP2A /kinetics/PP2A/PP2A_4E-BP_star ENZYME n
addmsg /kinetics/4E-BP_t37_46 /kinetics/PP2A/PP2A_4E-BP_star SUBSTRATE n
addmsg /kinetics/PP2A /kinetics/PP2A/PP2A_4E-BP ENZYME n
addmsg /kinetics/4E-BP_mod/eIF4E_4E-BP_t37_46_s65 /kinetics/PP2A/PP2A_4E-BP SUBSTRATE n
addmsg /kinetics/PP2A /kinetics/PP2A/PP2A_4EBP ENZYME n
addmsg /kinetics/4E-BP_mod/eIF4E-BP_thr37_46 /kinetics/PP2A/PP2A_4EBP SUBSTRATE n
addmsg /kinetics/AKT_mod/PIP3_bind_AKT /kinetics/AKT_mod/PIP3_AKT REAC B A
addmsg /kinetics/AKT_mod/PIP3_PDK1/phospho_thr308 /kinetics/AKT_mod/PIP3_AKT REAC sA B
addmsg /kinetics/PP2A/Dephosph_AKTthr308 /kinetics/AKT_mod/PIP3_AKT MM_PRD pA
addmsg /kinetics/AKT_mod/PIP3_bind_PDK1 /kinetics/AKT_mod/PIP3_PDK1 REAC B A
addmsg /kinetics/AKT_mod/PIP3_PDK1/phospho_thr308 /kinetics/AKT_mod/PIP3_PDK1 REAC eA B
addmsg /kinetics/AKT_mod/PIP3_PDK1 /kinetics/AKT_mod/PIP3_PDK1/phospho_thr308 ENZYME n
addmsg /kinetics/AKT_mod/PIP3_AKT /kinetics/AKT_mod/PIP3_PDK1/phospho_thr308 SUBSTRATE n
addmsg /kinetics/AKT_mod/PIP3_PDK2/phosp_AKTser473 /kinetics/AKT_mod/PIP3_PDK2 REAC eA B
addmsg /kinetics/AKT_mod/PIP3_PDK2 /kinetics/AKT_mod/PIP3_PDK2/phosp_AKTser473 ENZYME n
addmsg /kinetics/AKT_mod/PIP3_AKT_thr308 /kinetics/AKT_mod/PIP3_PDK2/phosp_AKTser473 SUBSTRATE n
addmsg /kinetics/AKT_mod/PIP3_PDK1/phospho_thr308 /kinetics/AKT_mod/PIP3_AKT_thr308 MM_PRD pA
addmsg /kinetics/AKT_mod/PIP3_PDK2/phosp_AKTser473 /kinetics/AKT_mod/PIP3_AKT_thr308 REAC sA B
addmsg /kinetics/PP2A/Dephos_AKTser473 /kinetics/AKT_mod/PIP3_AKT_thr308 MM_PRD pA
addmsg /kinetics/PP2A/Dephosph_AKTthr308 /kinetics/AKT_mod/PIP3_AKT_thr308 REAC sA B
addmsg /kinetics/AKT_mod/PIP3_PDK2/phosp_AKTser473 /kinetics/AKT_mod/PIP3_AKT-t308_s473 MM_PRD pA
addmsg /kinetics/PP2A/Dephos_AKTser473 /kinetics/AKT_mod/PIP3_AKT-t308_s473 REAC sA B
addmsg /kinetics/AKT_mod/PIP3_AKT-t308_s473/TSC2_phospho /kinetics/AKT_mod/PIP3_AKT-t308_s473 REAC eA B
addmsg /kinetics/AKT_mod/PIP3_AKT-t308_s473 /kinetics/AKT_mod/PIP3_AKT-t308_s473/TSC2_phospho ENZYME n
addmsg /kinetics/TSC1-TSC2 /kinetics/AKT_mod/PIP3_AKT-t308_s473/TSC2_phospho SUBSTRATE n
addmsg /kinetics/AKT_mod/PIP3_bind_AKT /kinetics/AKT_mod/AKT REAC A B
addmsg /kinetics/AKT_mod/PIP3_AKT-t308_s473/TSC2_phospho /kinetics/AKT_mod/TSC1-TSC2_star MM_PRD pA
addmsg /kinetics/AKT_mod/TSC1-2_dephospho /kinetics/AKT_mod/TSC1-TSC2_star REAC A B
addmsg /kinetics/AKT_mod/AKT /kinetics/AKT_mod/PIP3_bind_AKT SUBSTRATE n
addmsg /kinetics/PIP3 /kinetics/AKT_mod/PIP3_bind_AKT SUBSTRATE n
addmsg /kinetics/AKT_mod/PIP3_AKT /kinetics/AKT_mod/PIP3_bind_AKT PRODUCT n
addmsg /kinetics/PDK1 /kinetics/AKT_mod/PIP3_bind_PDK1 SUBSTRATE n
addmsg /kinetics/PIP3 /kinetics/AKT_mod/PIP3_bind_PDK1 SUBSTRATE n
addmsg /kinetics/AKT_mod/PIP3_PDK1 /kinetics/AKT_mod/PIP3_bind_PDK1 PRODUCT n
addmsg /kinetics/AKT_mod/TSC1-TSC2_star /kinetics/AKT_mod/TSC1-2_dephospho SUBSTRATE n
addmsg /kinetics/TSC1-TSC2 /kinetics/AKT_mod/TSC1-2_dephospho PRODUCT n
addmsg /kinetics/TrKB_mod/LR_Internalize /kinetics/TrKB_mod/Int_BDNF_TrKB2_star_clx REAC B A
addmsg /kinetics/TrKB_mod/LR_cycling /kinetics/TrKB_mod/Int_BDNF_TrKB2_star_clx REAC A B
addmsg /kinetics/TrKB_mod/LR_Internalize /kinetics/TrKB_mod/Int_BDNF_TrKB2_star_clx REAC B A
addmsg /kinetics/TrKB_mod/Ligand_binding /kinetics/TrKB_mod/TrKB REAC A B
addmsg /kinetics/TrKB_mod/Dimeriz_TrKB /kinetics/TrKB_mod/TrKB REAC A B
addmsg /kinetics/TrKB_mod/LR_cycling /kinetics/TrKB_mod/TrKB REAC B A
addmsg /kinetics/TrKB_mod/Dimeriz_TrKB /kinetics/TrKB_mod/BDNF_TrkB2_clx REAC B A
addmsg /kinetics/TrKB_mod/Autophos_TrKB /kinetics/TrKB_mod/BDNF_TrkB2_clx REAC A B
addmsg /kinetics/TrKB_mod/BDNF_TrkB2_star_clx /kinetics/TrKB_mod/Autophos_TrKB PRODUCT n
addmsg /kinetics/TrKB_mod/BDNF_TrkB2_clx /kinetics/TrKB_mod/Autophos_TrKB SUBSTRATE n
addmsg /kinetics/TrKB_mod/BDNF_TrkB2_clx /kinetics/TrKB_mod/Dimeriz_TrKB PRODUCT n
addmsg /kinetics/TrKB_mod/BDNF_TrkB_clx /kinetics/TrKB_mod/Dimeriz_TrKB SUBSTRATE n
addmsg /kinetics/TrKB_mod/TrKB /kinetics/TrKB_mod/Dimeriz_TrKB SUBSTRATE n
addmsg /kinetics/TrKB_mod/Ligand_binding /kinetics/TrKB_mod/BDNF_TrkB_clx REAC B A
addmsg /kinetics/TrKB_mod/Dimeriz_TrKB /kinetics/TrKB_mod/BDNF_TrkB_clx REAC A B
addmsg /kinetics/TrKB_mod/TrKB /kinetics/TrKB_mod/Ligand_binding SUBSTRATE n
addmsg /kinetics/BDNF /kinetics/TrKB_mod/Ligand_binding SUBSTRATE n
addmsg /kinetics/TrKB_mod/BDNF_TrkB_clx /kinetics/TrKB_mod/Ligand_binding PRODUCT n
addmsg /kinetics/TrKB_mod/Autophos_TrKB /kinetics/TrKB_mod/BDNF_TrkB2_star_clx REAC B A
addmsg /kinetics/TrKB_mod/BDNF_TrkB2_star_clx/PLC_g_phospho /kinetics/TrKB_mod/BDNF_TrkB2_star_clx REAC eA B
addmsg /kinetics/TrKB_mod/LR_Internalize /kinetics/TrKB_mod/BDNF_TrkB2_star_clx REAC A B
addmsg /kinetics/TrKB_mod/BDNF_TrkB2_star_clx/Shc_phospho /kinetics/TrKB_mod/BDNF_TrkB2_star_clx REAC eA B
addmsg /kinetics/TrKB_mod/BDNF_TrkB2_star_clx /kinetics/TrKB_mod/BDNF_TrkB2_star_clx/PLC_g_phospho ENZYME n
addmsg /kinetics/PLC_g /kinetics/TrKB_mod/BDNF_TrkB2_star_clx/PLC_g_phospho SUBSTRATE n
addmsg /kinetics/TrKB_mod/BDNF_TrkB2_star_clx /kinetics/TrKB_mod/BDNF_TrkB2_star_clx/Shc_phospho ENZYME n
addmsg /kinetics/PI3K_mod/Shc /kinetics/TrKB_mod/BDNF_TrkB2_star_clx/Shc_phospho SUBSTRATE n
addmsg /kinetics/PLC_g_star /kinetics/TrKB_mod/PLC_g_star_dephospho SUBSTRATE n
addmsg /kinetics/PLC_g /kinetics/TrKB_mod/PLC_g_star_dephospho PRODUCT n
addmsg /kinetics/PI3K_mod/PI3K_act /kinetics/TrKB_mod/Shc_star_Grb2-Gab1_PI3K_clx REAC B A
addmsg /kinetics/TrKB_mod/Shc_star_Grb2-Gab1_PI3K_clx/Phospho /kinetics/TrKB_mod/Shc_star_Grb2-Gab1_PI3K_clx REAC eA B
addmsg /kinetics/TrKB_mod/Shc_star_Grb2-Gab1_PI3K_clx /kinetics/TrKB_mod/Shc_star_Grb2-Gab1_PI3K_clx/Phospho ENZYME n
addmsg /kinetics/PI3K_mod/PIP2 /kinetics/TrKB_mod/Shc_star_Grb2-Gab1_PI3K_clx/Phospho SUBSTRATE n
addmsg /kinetics/TrKB_mod/Int_BDNF_TrKB2_star_clx /kinetics/TrKB_mod/LR_Internalize PRODUCT n
addmsg /kinetics/TrKB_mod/BDNF_TrkB2_star_clx /kinetics/TrKB_mod/LR_Internalize SUBSTRATE n
addmsg /kinetics/TrKB_mod/Int_BDNF_TrKB2_star_clx /kinetics/TrKB_mod/LR_Internalize PRODUCT n
addmsg /kinetics/TrKB_mod/Int_BDNF_TrKB2_star_clx /kinetics/TrKB_mod/LR_cycling SUBSTRATE n
addmsg /kinetics/TrKB_mod/TrKB /kinetics/TrKB_mod/LR_cycling PRODUCT n
addmsg /kinetics/PI3K_mod/PI3K_act /kinetics/PI3K_mod/PI3K REAC A B
addmsg /kinetics/PI3K_mod/basal_PI3K_act /kinetics/PI3K_mod/PI3K REAC A B
addmsg /kinetics/PI3K_bind_Ras-GTP /kinetics/PI3K_mod/PI3K REAC A B
addmsg /kinetics/PI3K_mod/PI3K_basal/basal_phosp /kinetics/PI3K_mod/PI3K_basal REAC eA B
addmsg /kinetics/PI3K_mod/basal_PI3K_act /kinetics/PI3K_mod/PI3K_basal REAC B A
addmsg /kinetics/PI3K_mod/PI3K_basal /kinetics/PI3K_mod/PI3K_basal/basal_phosp ENZYME n
addmsg /kinetics/PI3K_mod/PIP2 /kinetics/PI3K_mod/PI3K_basal/basal_phosp SUBSTRATE n
addmsg /kinetics/TrKB_mod/Shc_star_Grb2-Gab1_PI3K_clx/Phospho /kinetics/PI3K_mod/PIP2 REAC sA B
addmsg /kinetics/PI3K_mod/PI3K_basal/basal_phosp /kinetics/PI3K_mod/PIP2 REAC sA B
addmsg /kinetics/PTEN/PIP3_dephosp /kinetics/PI3K_mod/PIP2 MM_PRD pA
addmsg /kinetics/Ras-GTP_PI3K/PIP2_phospho_Ras-GTP /kinetics/PI3K_mod/PIP2 REAC sA B
addmsg /kinetics/TrKB_mod/BDNF_TrkB2_star_clx/Shc_phospho /kinetics/PI3K_mod/Shc REAC sA B
addmsg /kinetics/PI3K_mod/Shc_star_dephospho /kinetics/PI3K_mod/Shc REAC B A
addmsg /kinetics/Shc_star /kinetics/PI3K_mod/Shc_star_dephospho SUBSTRATE n
addmsg /kinetics/PI3K_mod/Shc /kinetics/PI3K_mod/Shc_star_dephospho PRODUCT n
addmsg /kinetics/Grb2 /kinetics/PI3K_mod/Grb2_bind_Shc SUBSTRATE n
addmsg /kinetics/Shc_star /kinetics/PI3K_mod/Grb2_bind_Shc SUBSTRATE n
addmsg /kinetics/PI3K_mod/Shc_star_Grb2_clx /kinetics/PI3K_mod/Grb2_bind_Shc PRODUCT n
addmsg /kinetics/PI3K_mod/Grb2_bind_Shc /kinetics/PI3K_mod/Shc_star_Grb2_clx REAC B A
addmsg /kinetics/PI3K_mod/bind_Gab1 /kinetics/PI3K_mod/Shc_star_Grb2_clx REAC A B
addmsg /kinetics/PI3K_mod/bind_Gab1 /kinetics/PI3K_mod/Gab1 REAC A B
addmsg /kinetics/PI3K_mod/Shc_star_Grb2-Gab1_clx /kinetics/PI3K_mod/bind_Gab1 PRODUCT n
addmsg /kinetics/PI3K_mod/Gab1 /kinetics/PI3K_mod/bind_Gab1 SUBSTRATE n
addmsg /kinetics/PI3K_mod/Shc_star_Grb2_clx /kinetics/PI3K_mod/bind_Gab1 SUBSTRATE n
addmsg /kinetics/PI3K_mod/bind_Gab1 /kinetics/PI3K_mod/Shc_star_Grb2-Gab1_clx REAC B A
addmsg /kinetics/PI3K_mod/PI3K_act /kinetics/PI3K_mod/Shc_star_Grb2-Gab1_clx REAC A B
addmsg /kinetics/PI3K_mod/PI3K /kinetics/PI3K_mod/PI3K_act SUBSTRATE n
addmsg /kinetics/TrKB_mod/Shc_star_Grb2-Gab1_PI3K_clx /kinetics/PI3K_mod/PI3K_act PRODUCT n
addmsg /kinetics/PI3K_mod/Shc_star_Grb2-Gab1_clx /kinetics/PI3K_mod/PI3K_act SUBSTRATE n
addmsg /kinetics/PI3K_mod/PI3K /kinetics/PI3K_mod/basal_PI3K_act SUBSTRATE n
addmsg /kinetics/PI3K_mod/PI3K_basal /kinetics/PI3K_mod/basal_PI3K_act PRODUCT n
addmsg /kinetics/PLCg_basal/PLC_g_phospho /kinetics/PLCg_basal REAC eA B
addmsg /kinetics/PLCg_basal /kinetics/PLCg_basal/PLC_g_phospho ENZYME n
addmsg /kinetics/PLC_g /kinetics/PLCg_basal/PLC_g_phospho SUBSTRATE n
addmsg /kinetics/AKT_mod/PIP3_AKT-t308_s473/TSC2_phospho /kinetics/TSC1-TSC2 REAC sA B
addmsg /kinetics/AKT_mod/TSC1-2_dephospho /kinetics/TSC1-TSC2 REAC B A
addmsg /kinetics/TSC1-TSC2/TSC2phospho /kinetics/TSC1-TSC2 REAC eA B
addmsg /kinetics/TSC1-TSC2 /kinetics/TSC1-TSC2/TSC2phospho ENZYME n
addmsg /kinetics/Rheb-GTP /kinetics/TSC1-TSC2/TSC2phospho SUBSTRATE n
addmsg /kinetics/4E-BP_mod/eIF4E-BP2_disso /kinetics/eIF4E REAC B A
addmsg /kinetics/eIF4F_clx /kinetics/eIF4E REAC A B
addmsg /kinetics/eIF4E-BP_disso /kinetics/eIF4E REAC B A
addmsg /kinetics/4E-BP_mod/eIF4E_bind_BP2 /kinetics/eIF4E REAC A B
addmsg /kinetics/TSC1-TSC2/TSC2phospho /kinetics/Rheb-GTP REAC sA B
addmsg /kinetics/GDP_to_GTP /kinetics/Rheb-GTP REAC B A
addmsg /kinetics/mTOR_model/Rheb-GTP_bind_TORclx /kinetics/Rheb-GTP REAC A B
addmsg /kinetics/TSC1-TSC2/TSC2phospho /kinetics/Rheb-GDP MM_PRD pA
addmsg /kinetics/GDP_to_GTP /kinetics/Rheb-GDP REAC A B
addmsg /kinetics/Rheb-GTP /kinetics/mTOR_model/Rheb-GTP_bind_TORclx SUBSTRATE n
addmsg /kinetics/mTOR_model/TOR-clx /kinetics/mTOR_model/Rheb-GTP_bind_TORclx SUBSTRATE n
addmsg /kinetics/TOR_Rheb-GTP_clx /kinetics/mTOR_model/Rheb-GTP_bind_TORclx PRODUCT n
addmsg /kinetics/mTOR_model/Rheb-GTP_bind_TORclx /kinetics/mTOR_model/TOR-clx REAC A B
addmsg /kinetics/mTOR_model/Rheb-GTP_bind_TORclx /kinetics/TOR_Rheb-GTP_clx REAC B A
addmsg /kinetics/TOR_Rheb-GTP_clx/S6K_phospho /kinetics/TOR_Rheb-GTP_clx REAC eA B
addmsg /kinetics/TOR_Rheb-GTP_clx/TOR_4E-BP_phospho /kinetics/TOR_Rheb-GTP_clx REAC eA B
addmsg /kinetics/TOR_Rheb-GTP_clx/TOR_4E-BP_star /kinetics/TOR_Rheb-GTP_clx REAC eA B
addmsg /kinetics/TOR_Rheb-GTP_clx /kinetics/TOR_Rheb-GTP_clx/S6K_phospho ENZYME n
addmsg /kinetics/S6Kinase/S6K_star /kinetics/TOR_Rheb-GTP_clx/S6K_phospho SUBSTRATE n
addmsg /kinetics/TOR_Rheb-GTP_clx /kinetics/TOR_Rheb-GTP_clx/TOR_4E-BP_phospho ENZYME n
addmsg /kinetics/4E-BP_mod/eIF4E-BP /kinetics/TOR_Rheb-GTP_clx/TOR_4E-BP_phospho SUBSTRATE n
addmsg /kinetics/TOR_Rheb-GTP_clx /kinetics/TOR_Rheb-GTP_clx/TOR_4E-BP_star ENZYME n
addmsg /kinetics/4E-BP_mod/4E-BP /kinetics/TOR_Rheb-GTP_clx/TOR_4E-BP_star SUBSTRATE n
addmsg /kinetics/MAPK_star/cluster_phospho_S6K /kinetics/S6Kinase/S6K_star MM_PRD pA
addmsg /kinetics/TOR_Rheb-GTP_clx/S6K_phospho /kinetics/S6Kinase/S6K_star REAC sA B
addmsg /kinetics/PP2A/dephos_S6K /kinetics/S6Kinase/S6K_star MM_PRD pA
addmsg /kinetics/PP2A/dephos_clus_S6K /kinetics/S6Kinase/S6K_star REAC sA B
addmsg /kinetics/basal_S6K /kinetics/S6Kinase/S6K_star REAC B A
addmsg /kinetics/MAPK_star/cluster_phospho_S6K /kinetics/S6Kinase/S6K REAC sA B
addmsg /kinetics/PP2A/dephos_clus_S6K /kinetics/S6Kinase/S6K MM_PRD pA
addmsg /kinetics/basal_S6K /kinetics/S6Kinase/S6K REAC A B
addmsg /kinetics/TOR_Rheb-GTP_clx/S6K_phospho /kinetics/S6Kinase/S6K_thr-412 MM_PRD pA
addmsg /kinetics/PDK1/S6K_phospho /kinetics/S6Kinase/S6K_thr-412 REAC sA B
addmsg /kinetics/PP2A/dephosp_S6K /kinetics/S6Kinase/S6K_thr-412 MM_PRD pA
addmsg /kinetics/PP2A/dephos_S6K /kinetics/S6Kinase/S6K_thr-412 REAC sA B
addmsg /kinetics/S6Kinase/S6K_thr-412/S6_phos /kinetics/S6Kinase/S6K_thr-412 REAC eA B
addmsg /kinetics/S6Kinase/S6K_thr-412 /kinetics/S6Kinase/S6K_thr-412/S6_phos ENZYME n
addmsg /kinetics/S6Kinase/40S_inact /kinetics/S6Kinase/S6K_thr-412/S6_phos SUBSTRATE n
addmsg /kinetics/40S /kinetics/S6Kinase/S6_dephosph SUBSTRATE n
addmsg /kinetics/S6Kinase/40S_inact /kinetics/S6Kinase/S6_dephosph PRODUCT n
addmsg /kinetics/S6Kinase/S6_dephosph /kinetics/S6Kinase/40S_inact REAC B A
addmsg /kinetics/S6K_thr-252/S6_phospho /kinetics/S6Kinase/40S_inact REAC sA B
addmsg /kinetics/40S_basal/basal /kinetics/S6Kinase/40S_inact REAC sA B
addmsg /kinetics/S6Kinase/S6K_thr-412/S6_phos /kinetics/S6Kinase/40S_inact REAC sA B
addmsg /kinetics/4E-BP_mod/4E-BP /kinetics/4E-BP_mod/eIF4E_bind_BP2 SUBSTRATE n
addmsg /kinetics/eIF4E /kinetics/4E-BP_mod/eIF4E_bind_BP2 SUBSTRATE n
addmsg /kinetics/4E-BP_mod/eIF4E-BP /kinetics/4E-BP_mod/eIF4E_bind_BP2 PRODUCT n
addmsg /kinetics/eIF4E /kinetics/4E-BP_mod/eIF4E-BP2_disso PRODUCT n
addmsg /kinetics/4E-BP_mod/eIF4E_4E-BP_t37_46_s65 /kinetics/4E-BP_mod/eIF4E-BP2_disso SUBSTRATE n
addmsg /kinetics/4E-BP_mod/4E-BP_thr37_46_s65 /kinetics/4E-BP_mod/eIF4E-BP2_disso PRODUCT n
addmsg /kinetics/TOR_Rheb-GTP_clx/TOR_4E-BP_star /kinetics/4E-BP_mod/4E-BP REAC sA B
addmsg /kinetics/PP2A/PP2A_4E-BP_star /kinetics/4E-BP_mod/4E-BP MM_PRD pA
addmsg /kinetics/4E-BP_mod/eIF4E_bind_BP2 /kinetics/4E-BP_mod/4E-BP REAC A B
addmsg /kinetics/4E-BP_mod/eIF4E-BP2_disso /kinetics/4E-BP_mod/4E-BP_thr37_46_s65 REAC B A
addmsg /kinetics/MAPK_star/MAPK_4E-BP_star_star /kinetics/4E-BP_mod/4E-BP_thr37_46_s65 MM_PRD pA
addmsg /kinetics/PP2A/PP2A_4E-BP_star_star /kinetics/4E-BP_mod/4E-BP_thr37_46_s65 REAC sA B
addmsg /kinetics/TOR_Rheb-GTP_clx/TOR_4E-BP_phospho /kinetics/4E-BP_mod/eIF4E-BP REAC sA B
addmsg /kinetics/PP2A/PP2A_4EBP /kinetics/4E-BP_mod/eIF4E-BP MM_PRD pA
addmsg /kinetics/4E-BP_mod/eIF4E_bind_BP2 /kinetics/4E-BP_mod/eIF4E-BP REAC B A
addmsg /kinetics/TOR_Rheb-GTP_clx/TOR_4E-BP_phospho /kinetics/4E-BP_mod/eIF4E-BP_thr37_46 MM_PRD pA
addmsg /kinetics/PP2A/PP2A_4EBP /kinetics/4E-BP_mod/eIF4E-BP_thr37_46 REAC sA B
addmsg /kinetics/MAPK_star/MAPK_4E-BP_phospho /kinetics/4E-BP_mod/eIF4E-BP_thr37_46 REAC sA B
addmsg /kinetics/PP2A/PP2A_4E-BP /kinetics/4E-BP_mod/eIF4E-BP_thr37_46 MM_PRD pA
addmsg /kinetics/eIF4E-BP_disso /kinetics/4E-BP_mod/eIF4E-BP_thr37_46 REAC A B
addmsg /kinetics/MAPK_star/MAPK_4E-BP_phospho /kinetics/4E-BP_mod/eIF4E_4E-BP_t37_46_s65 MM_PRD pA
addmsg /kinetics/PP2A/PP2A_4E-BP /kinetics/4E-BP_mod/eIF4E_4E-BP_t37_46_s65 REAC sA B
addmsg /kinetics/4E-BP_mod/eIF4E-BP2_disso /kinetics/4E-BP_mod/eIF4E_4E-BP_t37_46_s65 REAC A B
addmsg /kinetics/S6Kinase/S6_dephosph /kinetics/40S REAC A B
addmsg /kinetics/S6K_thr-252/S6_phospho /kinetics/40S MM_PRD pA
addmsg /kinetics/43S_complex/Q_binds_R /kinetics/40S REAC A B
addmsg /kinetics/43S_complex/R_binds_M /kinetics/40S REAC A B
addmsg /kinetics/40S_basal/basal /kinetics/40S MM_PRD pA
addmsg /kinetics/S6Kinase/S6K_thr-412/S6_phos /kinetics/40S MM_PRD pA
addmsg /kinetics/eIF4G-A_clx /kinetics/eIF4F_clx SUBSTRATE n
addmsg /kinetics/eIF4F /kinetics/eIF4F_clx PRODUCT n
addmsg /kinetics/eIF4E /kinetics/eIF4F_clx SUBSTRATE n
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addmsg /kinetics/PI3K_bind_Ras-GTP /kinetics/Ras/GTP-Ras REAC A B
addmsg /kinetics/Ras/GAP/GAP-inact-ras /kinetics/Ras/GDP-Ras MM_PRD pA
addmsg /kinetics/Ras/Ras-intrinsic-GTPase /kinetics/Ras/GDP-Ras REAC B A
addmsg /kinetics/Ras/GEF_star/GEF_star-act-ras /kinetics/Ras/GDP-Ras REAC sA B
addmsg /kinetics/Ras/CaM-GEF/CaM-GEF-act-ras /kinetics/Ras/GDP-Ras REAC sA B
addmsg /kinetics/Shc_star.Sos.Grb2/Sos.Ras_GEF /kinetics/Ras/GDP-Ras REAC sA B
addmsg /kinetics/Ras/inact-GEF/basal_GEF_activity /kinetics/Ras/GDP-Ras REAC sA B
addmsg /kinetics/Ras/GTP-Ras /kinetics/Ras/Ras-intrinsic-GTPase SUBSTRATE n
addmsg /kinetics/Ras/GDP-Ras /kinetics/Ras/Ras-intrinsic-GTPase PRODUCT n
addmsg /kinetics/Ras/GAP_star /kinetics/Ras/dephosph-GAP SUBSTRATE n
addmsg /kinetics/Ras/GAP /kinetics/Ras/dephosph-GAP PRODUCT n
addmsg /kinetics/PKC-active/PKC-inact-GAP /kinetics/Ras/GAP_star MM_PRD pA
addmsg /kinetics/Ras/dephosph-GAP /kinetics/Ras/GAP_star REAC A B
addmsg /kinetics/Ras/GAP/GAP-inact-ras /kinetics/Ras/GAP REAC eA B
addmsg /kinetics/PKC-active/PKC-inact-GAP /kinetics/Ras/GAP REAC sA B
addmsg /kinetics/Ras/dephosph-GAP /kinetics/Ras/GAP REAC B A
addmsg /kinetics/Ras/GAP /kinetics/Ras/GAP/GAP-inact-ras ENZYME n
addmsg /kinetics/Ras/GTP-Ras /kinetics/Ras/GAP/GAP-inact-ras SUBSTRATE n
addmsg /kinetics/Ras/inact-GEF /kinetics/Ras/CaM-bind-GEF SUBSTRATE n
addmsg /kinetics/Ras/CaM-GEF /kinetics/Ras/CaM-bind-GEF PRODUCT n
addmsg /kinetics/CaM-Ca4 /kinetics/Ras/CaM-bind-GEF SUBSTRATE n
addmsg /kinetics/Ras/CaM-bind-GEF /kinetics/Ras/CaM-GEF REAC B A
addmsg /kinetics/Ras/CaM-GEF/CaM-GEF-act-ras /kinetics/Ras/CaM-GEF REAC eA B
addmsg /kinetics/Ras/CaM-GEF /kinetics/Ras/CaM-GEF/CaM-GEF-act-ras ENZYME n
addmsg /kinetics/Ras/GDP-Ras /kinetics/Ras/CaM-GEF/CaM-GEF-act-ras SUBSTRATE n
addmsg /kinetics/Sos/Shc_bind_Sos.Grb2 /kinetics/Shc_star.Sos.Grb2 REAC B A
addmsg /kinetics/Shc_star.Sos.Grb2/Sos.Ras_GEF /kinetics/Shc_star.Sos.Grb2 REAC eA B
addmsg /kinetics/Shc_star.Sos.Grb2 /kinetics/Shc_star.Sos.Grb2/Sos.Ras_GEF ENZYME n
addmsg /kinetics/Ras/GDP-Ras /kinetics/Shc_star.Sos.Grb2/Sos.Ras_GEF SUBSTRATE n
addmsg /kinetics/Sos/Sos.Grb2 /kinetics/Sos/Shc_bind_Sos.Grb2 SUBSTRATE n
addmsg /kinetics/Shc_star /kinetics/Sos/Shc_bind_Sos.Grb2 SUBSTRATE n
addmsg /kinetics/Shc_star.Sos.Grb2 /kinetics/Sos/Shc_bind_Sos.Grb2 PRODUCT n
addmsg /kinetics/Sos/Grb2_bind_Sos_star /kinetics/Sos/Sos_star.Grb2 REAC B A
addmsg /kinetics/Sos/Sos_star /kinetics/Sos/Grb2_bind_Sos_star SUBSTRATE n
addmsg /kinetics/Grb2 /kinetics/Sos/Grb2_bind_Sos_star SUBSTRATE n
addmsg /kinetics/Sos/Sos_star.Grb2 /kinetics/Sos/Grb2_bind_Sos_star PRODUCT n
addmsg /kinetics/Sos/Grb2_bind_Sos /kinetics/Sos/Sos.Grb2 REAC B A
addmsg /kinetics/Sos/Shc_bind_Sos.Grb2 /kinetics/Sos/Sos.Grb2 REAC A B
addmsg /kinetics/MAPK_star/phosph_Sos /kinetics/Sos/Sos_star MM_PRD pA
addmsg /kinetics/Sos/Grb2_bind_Sos_star /kinetics/Sos/Sos_star REAC A B
addmsg /kinetics/Sos/dephosph_Sos /kinetics/Sos/Sos_star REAC A B
addmsg /kinetics/Sos/Sos_star /kinetics/Sos/dephosph_Sos SUBSTRATE n
addmsg /kinetics/Sos/Sos /kinetics/Sos/dephosph_Sos PRODUCT n
addmsg /kinetics/Grb2 /kinetics/Sos/Grb2_bind_Sos SUBSTRATE n
addmsg /kinetics/Sos/Sos.Grb2 /kinetics/Sos/Grb2_bind_Sos PRODUCT n
addmsg /kinetics/Sos/Sos /kinetics/Sos/Grb2_bind_Sos SUBSTRATE n
addmsg /kinetics/Sos/Grb2_bind_Sos /kinetics/Sos/Sos REAC A B
addmsg /kinetics/MAPK_star/phosph_Sos /kinetics/Sos/Sos REAC sA B
addmsg /kinetics/Sos/dephosph_Sos /kinetics/Sos/Sos REAC B A
addmsg /kinetics/43S_complex/QR_binds_M /kinetics/43Scomplex REAC B A
addmsg /kinetics/43S_complex/RM_binds_Q /kinetics/43Scomplex REAC B A
addmsg /kinetics/activation /kinetics/43Scomplex REAC A B
addmsg /kinetics/CaM-Ca4 /kinetics/CaMKIII_bind_CaM-Ca4 SUBSTRATE n
addmsg /kinetics/CaMKIII /kinetics/CaMKIII_bind_CaM-Ca4 SUBSTRATE n
addmsg /kinetics/CaMKIII_CaM-Ca4 /kinetics/CaMKIII_bind_CaM-Ca4 PRODUCT n
addmsg /kinetics/protein /kinetics/pep_elongation PRODUCT n
addmsg /kinetics/peptide /kinetics/pep_elongation SUBSTRATE n
addmsg /kinetics/degraded_protein /kinetics/protein_deg PRODUCT n
addmsg /kinetics/protein /kinetics/protein_deg SUBSTRATE n
addmsg /kinetics/Rheb-GDP /kinetics/GDP_to_GTP SUBSTRATE n
addmsg /kinetics/Rheb-GTP /kinetics/GDP_to_GTP PRODUCT n
addmsg /kinetics/PKC/PKC-act-by-Ca /kinetics/PKC/PKC-Ca REAC B A
addmsg /kinetics/PKC/PKC-act-by-DAG /kinetics/PKC/PKC-Ca REAC A B
addmsg /kinetics/PKC/PKC-Ca-to-memb /kinetics/PKC/PKC-Ca REAC A B
addmsg /kinetics/PKC/PKC-act-by-Ca-AA /kinetics/PKC/PKC-Ca REAC A B
addmsg /kinetics/PKC/PKC-cytosolic /kinetics/PKC/PKC-act-by-Ca SUBSTRATE n
addmsg /kinetics/Ca /kinetics/PKC/PKC-act-by-Ca SUBSTRATE n
addmsg /kinetics/PKC/PKC-Ca /kinetics/PKC/PKC-act-by-Ca PRODUCT n
addmsg /kinetics/DAG /kinetics/PKC/PKC-act-by-DAG SUBSTRATE n
addmsg /kinetics/PKC/PKC-Ca /kinetics/PKC/PKC-act-by-DAG SUBSTRATE n
addmsg /kinetics/PKC/PKC-Ca-DAG /kinetics/PKC/PKC-act-by-DAG PRODUCT n
addmsg /kinetics/PKC/PKC-Ca /kinetics/PKC/PKC-Ca-to-memb SUBSTRATE n
addmsg /kinetics/PKC/PKC-Ca-memb_star /kinetics/PKC/PKC-Ca-to-memb PRODUCT n
addmsg /kinetics/PKC/PKC-Ca-DAG /kinetics/PKC/PKC-DAG-to-memb SUBSTRATE n
addmsg /kinetics/PKC/PKC-DAG-memb_star /kinetics/PKC/PKC-DAG-to-memb PRODUCT n
addmsg /kinetics/PKC/PKC-Ca /kinetics/PKC/PKC-act-by-Ca-AA SUBSTRATE n
addmsg /kinetics/Arachidonic_Acid /kinetics/PKC/PKC-act-by-Ca-AA SUBSTRATE n
addmsg /kinetics/PKC/PKC-Ca-AA_star /kinetics/PKC/PKC-act-by-Ca-AA PRODUCT n
addmsg /kinetics/PKC/PKC-DAG-AA_star /kinetics/PKC/PKC-act-by-DAG-AA PRODUCT n
addmsg /kinetics/PKC/PKC-DAG-AA /kinetics/PKC/PKC-act-by-DAG-AA SUBSTRATE n
addmsg /kinetics/PKC/PKC-act-by-DAG-AA /kinetics/PKC/PKC-DAG-AA_star REAC B A
addmsg /kinetics/PKC/PKC-act-by-Ca-AA /kinetics/PKC/PKC-Ca-AA_star REAC B A
addmsg /kinetics/PKC/PKC-Ca-to-memb /kinetics/PKC/PKC-Ca-memb_star REAC B A
addmsg /kinetics/PKC/PKC-DAG-to-memb /kinetics/PKC/PKC-DAG-memb_star REAC B A
addmsg /kinetics/PKC/PKC-basal-act /kinetics/PKC/PKC-basal_star REAC B A
addmsg /kinetics/PKC/PKC-cytosolic /kinetics/PKC/PKC-basal-act SUBSTRATE n
addmsg /kinetics/PKC/PKC-basal_star /kinetics/PKC/PKC-basal-act PRODUCT n
addmsg /kinetics/PKC/PKC-act-by-AA /kinetics/PKC/PKC-AA_star REAC B A
addmsg /kinetics/Arachidonic_Acid /kinetics/PKC/PKC-act-by-AA SUBSTRATE n
addmsg /kinetics/PKC/PKC-AA_star /kinetics/PKC/PKC-act-by-AA PRODUCT n
addmsg /kinetics/PKC/PKC-cytosolic /kinetics/PKC/PKC-act-by-AA SUBSTRATE n
addmsg /kinetics/PKC/PKC-act-by-DAG /kinetics/PKC/PKC-Ca-DAG REAC B A
addmsg /kinetics/PKC/PKC-DAG-to-memb /kinetics/PKC/PKC-Ca-DAG REAC A B
addmsg /kinetics/PKC/PKC-cytosolic /kinetics/PKC/PKC-n-DAG SUBSTRATE n
addmsg /kinetics/DAG /kinetics/PKC/PKC-n-DAG SUBSTRATE n
addmsg /kinetics/PKC/PKC-DAG /kinetics/PKC/PKC-n-DAG PRODUCT n
addmsg /kinetics/PKC/PKC-n-DAG /kinetics/PKC/PKC-DAG REAC B A
addmsg /kinetics/PKC/PKC-n-DAG-AA /kinetics/PKC/PKC-DAG REAC A B
addmsg /kinetics/PKC/PKC-DAG /kinetics/PKC/PKC-n-DAG-AA SUBSTRATE n
addmsg /kinetics/Arachidonic_Acid /kinetics/PKC/PKC-n-DAG-AA SUBSTRATE n
addmsg /kinetics/PKC/PKC-DAG-AA /kinetics/PKC/PKC-n-DAG-AA PRODUCT n
addmsg /kinetics/PKC/PKC-n-DAG-AA /kinetics/PKC/PKC-DAG-AA REAC B A
addmsg /kinetics/PKC/PKC-act-by-DAG-AA /kinetics/PKC/PKC-DAG-AA REAC A B
addmsg /kinetics/PKC/PKC-act-by-Ca /kinetics/PKC/PKC-cytosolic REAC A B
addmsg /kinetics/PKC/PKC-basal-act /kinetics/PKC/PKC-cytosolic REAC A B
addmsg /kinetics/PKC/PKC-act-by-AA /kinetics/PKC/PKC-cytosolic REAC A B
addmsg /kinetics/PKC/PKC-n-DAG /kinetics/PKC/PKC-cytosolic REAC A B
addmsg /kinetics/PKC/PKC-act-by-DAG /kinetics/DAG REAC A B
addmsg /kinetics/PKC/PKC-n-DAG /kinetics/DAG REAC A B
addmsg /kinetics/PKC/PKC-act-by-Ca-AA /kinetics/Arachidonic_Acid REAC A B
addmsg /kinetics/PKC/PKC-act-by-AA /kinetics/Arachidonic_Acid REAC A B
addmsg /kinetics/PKC/PKC-n-DAG-AA /kinetics/Arachidonic_Acid REAC A B
addmsg /kinetics/Basal_Translation/basal_syn /kinetics/Basal_Translation REAC eA B
addmsg /kinetics/Basal_Translation/rad_basal_syn /kinetics/Basal_Translation REAC eA B
addmsg /kinetics/Basal_Translation /kinetics/Basal_Translation/basal_syn ENZYME n
addmsg /kinetics/AA /kinetics/Basal_Translation/basal_syn SUBSTRATE n
addmsg /kinetics/Basal_Translation /kinetics/Basal_Translation/rad_basal_syn ENZYME n
addmsg /kinetics/rad_AA /kinetics/Basal_Translation/rad_basal_syn SUBSTRATE n
addmsg /kinetics/4E-BP_mod/eIF4E-BP_thr37_46 /kinetics/eIF4E-BP_disso SUBSTRATE n
addmsg /kinetics/4E-BP_t37_46 /kinetics/eIF4E-BP_disso PRODUCT n
addmsg /kinetics/eIF4E /kinetics/eIF4E-BP_disso PRODUCT n
addmsg /kinetics/S6Kinase/S6K /kinetics/basal_S6K SUBSTRATE n
addmsg /kinetics/S6Kinase/S6K_star /kinetics/basal_S6K PRODUCT n
addmsg /kinetics/labelling /kinetics/rad_AA REAC B A
addmsg /kinetics/Translation_clx/rad_pro_syn /kinetics/rad_AA REAC sA B
addmsg /kinetics/Basal_Translation/rad_basal_syn /kinetics/rad_AA REAC sA B
addmsg /kinetics/Translation_clx/rad_pro_syn /kinetics/rad_peptide MM_PRD pA
addmsg /kinetics/rad_pep_elongation /kinetics/rad_peptide REAC A B
addmsg /kinetics/rad_peptide /kinetics/rad_pep_elongation SUBSTRATE n
addmsg /kinetics/rad_protein /kinetics/rad_pep_elongation PRODUCT n
addmsg /kinetics/rad_pep_elongation /kinetics/rad_protein REAC B A
addmsg /kinetics/rad_protein_deg /kinetics/rad_protein REAC A B
addmsg /kinetics/rad_protein /kinetics/rad_protein_deg SUBSTRATE n
addmsg /kinetics/rad_deg_pro /kinetics/rad_protein_deg PRODUCT n
addmsg /kinetics/rad_protein_deg /kinetics/rad_deg_pro REAC B A
addmsg /kinetics/AA /kinetics/labelling SUBSTRATE n
addmsg /kinetics/rad_AA /kinetics/labelling PRODUCT n
addmsg /kinetics/40S_basal/basal /kinetics/40S_basal REAC eA B
addmsg /kinetics/40S_basal /kinetics/40S_basal/basal ENZYME n
addmsg /kinetics/S6Kinase/40S_inact /kinetics/40S_basal/basal SUBSTRATE n
addmsg /kinetics/eIF4E-BP_disso /kinetics/4E-BP_t37_46 REAC B A
addmsg /kinetics/MAPK_star/MAPK_4E-BP_star_star /kinetics/4E-BP_t37_46 REAC sA B
addmsg /kinetics/PP2A/PP2A_4E-BP_star_star /kinetics/4E-BP_t37_46 MM_PRD pA
addmsg /kinetics/TOR_Rheb-GTP_clx/TOR_4E-BP_star /kinetics/4E-BP_t37_46 MM_PRD pA
addmsg /kinetics/PP2A/PP2A_4E-BP_star /kinetics/4E-BP_t37_46 REAC sA B
addmsg /kinetics/PTEN/PIP3_dephosp /kinetics/PTEN REAC eA B
addmsg /kinetics/PTEN /kinetics/PTEN/PIP3_dephosp ENZYME n
addmsg /kinetics/PIP3 /kinetics/PTEN/PIP3_dephosp SUBSTRATE n
addmsg /kinetics/PI3K_bind_Ras-GTP /kinetics/Ras-GTP_PI3K REAC B A
addmsg /kinetics/Ras-GTP_PI3K/PIP2_phospho_Ras-GTP /kinetics/Ras-GTP_PI3K REAC eA B
addmsg /kinetics/Ras-GTP_PI3K /kinetics/Ras-GTP_PI3K/PIP2_phospho_Ras-GTP ENZYME n
addmsg /kinetics/PI3K_mod/PIP2 /kinetics/Ras-GTP_PI3K/PIP2_phospho_Ras-GTP SUBSTRATE n
addmsg /kinetics/Ras/GTP-Ras /kinetics/PI3K_bind_Ras-GTP SUBSTRATE n
addmsg /kinetics/PI3K_mod/PI3K /kinetics/PI3K_bind_Ras-GTP SUBSTRATE n
addmsg /kinetics/Ras-GTP_PI3K /kinetics/PI3K_bind_Ras-GTP PRODUCT n
addmsg /kinetics/40S /graphs/conc1/40S.Co PLOT Co *40S.Co *50
addmsg /kinetics/protein /graphs/conc1/protein.Co PLOT Co *protein.Co *red
addmsg /kinetics/MAPK_star /graphs/conc1/MAPK_star.Co PLOT Co *MAPK_star.Co *orange
addmsg /kinetics/eIF4E /graphs/conc1/eIF4E.Co PLOT Co *eIF4E.Co *42
addmsg /kinetics/eIF4F-mRNA_clx /graphs/conc1/eIF4F-mRNA_clx.Co PLOT Co *eIF4F-mRNA_clx.Co *59
addmsg /kinetics/eIF4F /graphs/conc1/eIF4F.Co PLOT Co *eIF4F.Co *6
addmsg /kinetics/S6K_thr-252 /graphs/conc1/S6K_thr-252.Co PLOT Co *S6K_thr-252.Co *6
addmsg /kinetics/AKT_mod/TSC1-TSC2_star /graphs/conc1/TSC1-TSC2_star.Co PLOT Co *TSC1-TSC2_star.Co *40
addmsg /kinetics/TrKB_mod/BDNF_TrkB2_star_clx /graphs/conc2/BDNF_TrkB2_star_clx.Co PLOT Co *BDNF_TrkB2_star_clx.Co *red
addmsg /kinetics/43Scomplex /graphs/conc2/43Scomplex.Co PLOT Co *43Scomplex.Co *hotpink
addmsg /kinetics/AKT_mod/PIP3_AKT-t308_s473 /graphs/conc2/PIP3_AKT-t308_s473.Co PLOT Co *PIP3_AKT-t308_s473.Co *25
addmsg /kinetics/degraded_protein /graphs/conc2/degraded_protein.Co PLOT Co *degraded_protein.Co *white
addmsg /kinetics/4E-BP_mod/eIF4E-BP /graphs/conc2/eIF4E-BP.Co PLOT Co *eIF4E-BP.Co *52
addmsg /kinetics/4E-BP_mod/eIF4E_4E-BP_t37_46_s65 /graphs/conc2/eIF4E_4E-BP_t37_46_s65.Co PLOT Co *eIF4E_4E-BP_t37_46_s65.Co *39
enddump
// End of dump
call /kinetics/PP2A/notes LOAD \
"Protein Phosphatase"
call /kinetics/AKT_mod/PIP3_AKT-t308_s473/notes LOAD \
"aaa"
call /kinetics/S6Kinase/S6K_star/notes LOAD \
"" \
"" \
""
call /kinetics/S6Kinase/40S_inact/notes LOAD \
"Inactivated form of S6K" \
""
call /kinetics/40S/notes LOAD \
"Activated form of S6" \
""
call /kinetics/43S_complex/Q.R/notes LOAD \
"Q.R= Quaternary complex.Ribosome" \
""
call /kinetics/43S_complex/Quaternary_clx/notes LOAD \
"Q= Quaternary complex" \
""
call /kinetics/CaM/CaM/notes LOAD \
"There is a LOT of this in the cell: upto 1% of total protein mass. (Alberts et al)" \
"Say 25 uM. Meyer et al Science 256 1199-1202 1992 refer to studies saying" \
"it is comparable to CaMK levels. " \
""
call /kinetics/CaM/CaM-Ca3-bind-Ca/notes LOAD \
"Use K3 = 21.5 uM here from Stemmer and Klee table 3." \
"kb/kf =21.5 * 6e5 so kf = 7.75e-7, kb = 10"
call /kinetics/CaM/CaM-bind-Ca/notes LOAD \
"Lets use the fast rate consts here. Since the rates are so different, I am not" \
"sure whether the order is relevant. These correspond to the TR2C fragment." \
"We use the Martin et al rates here, plus the Drabicowski binding consts." \
"All are scaled by 3X to cell temp." \
"kf = 2e-10 kb = 72" \
"Stemmer & Klee: K1=.9, K2=1.1. Assume 1.0uM for both. kb/kf=3.6e11." \
"If kb=72, kf = 2e-10 (Exactly the same !)" \
"" \
"19 May 2006. Splitting the old CaM-TR2-bind-Ca reaction into" \
"two steps, each binding 1 Ca. This improves numerical" \
"stability and is conceptually better too." \
"" \
"Overall rates are the same, so each kf and kb is the " \
"square root of the earlier ones. So" \
"kf = 1.125e-4, kb = 8.4853" \
""
call /kinetics/CaM/CaM-Ca2/notes LOAD \
"This is the intermediate where the TR2 end (the high-affinity end) has" \
"bound the Ca but the TR1 end has not."
call /kinetics/CaM/CaM-Ca2-bind-Ca/notes LOAD \
"K3 = 21.5, K4 = 2.8. Assuming that the K4 step happens first, we get" \
"kb/kf = 2.8 uM = 1.68e6 so kf =6e-6 assuming kb = 10" \
""
call /kinetics/CaM/CaM-Ca-bind-Ca/notes LOAD \
"Lets use the fast rate consts here. Since the rates are so different, I am not" \
"sure whether the order is relevant. These correspond to the TR2C fragment." \
"We use the Martin et al rates here, plus the Drabicowski binding consts." \
"All are scaled by 3X to cell temp." \
"kf = 2e-10 kb = 72" \
"Stemmer & Klee: K1=.9, K2=1.1. Assume 1.0uM for both. kb/kf=3.6e11." \
"If kb=72, kf = 2e-10 (Exactly the same !)" \
"" \
"19 May 2006. Splitting the old CaM-TR2-bind-Ca reaction into" \
"two steps, each binding 1 Ca. This improves numerical" \
"stability and is conceptually better too." \
"" \
"Overall rates are the same, so each kf and kb is the " \
"square root of the earlier ones. So" \
"kf = 1.125e-4, kb = 8.4853" \
""
call /kinetics/CaM/CaM-Ca/notes LOAD \
"This is the intermediate where the TR2 end (the high-affinity end) has" \
"bound the Ca but the TR1 end has not."
call /kinetics/Grb2/notes LOAD \
"There is probably a lot of it in the cell: it is also known" \
"as Ash (abundant src homology protein I think). Also " \
"Waters et al JBC 271:30 18224 1996 say that only a small" \
"fraction of cellular Grb is precipitated out when SoS is" \
"precipitated. As most of the Sos seems to be associated" \
"with Grb2, it would seem like there is a lot of the latter." \
"Say 1 uM. I haven't been able to find a decent...."
call /kinetics/MAPK_star/MAPK_star-feedback/notes LOAD \
"Ueki et al JBC 269(22):15756-15761 show the presence of" \
"this step, but not the rate consts, which are derived from" \
"Sanghera et al JBC 265(1):52-57, 1990, see the deriv in the" \
"MAPK_star notes."
call /kinetics/MAPK_star/phosph_Sos/notes LOAD \
"See Porfiri and McCormick JBC 271:10 pp5871 1996 for the" \
"existence of this step. We'll take the rates from the ones" \
"used for the phosph of Raf by MAPK." \
"Sep 17 1997: The transient activation curve matches better" \
"with k1 up by 10 x."
call /kinetics/PKC-active/notes LOAD \
"Conc of PKC in brain is about 1 uM (?)"
call /kinetics/PKC-active/PKC-act-raf/notes LOAD \
"Rate consts from Chen et al Biochem 32, 1032 (1993)" \
"k3 = k2 = 4" \
"k1 = 9e-5" \
"recalculated gives 1.666e-5, which is not very different." \
"Looks like k3 is rate-limiting in this case: there is a huge amount" \
"of craf locked up in the enz complex. Let us assume a 10x" \
"higher Km, ie, lower affinity. k1 drops by 10x." \
"Also changed k2 to 4x k3." \
"Lowerd k1 to 1e-6 to balance 10X DAG sensitivity of PKC"
call /kinetics/PKC-active/PKC-inact-GAP/notes LOAD \
"Rate consts copied from PCK-act-raf" \
"This reaction inactivates GAP. The idea is from the " \
"Boguski and McCormick review."
call /kinetics/PKC-active/PKC-act-GEF/notes LOAD \
"Rate consts from PKC-act-raf." \
"This reaction activates GEF. It can lead to at least 2X stim of ras, and" \
"a 2X stim of MAPK over and above that obtained via direct phosph of" \
"c-raf. Note that it is a push-pull reaction, and there is also a contribution" \
"through the phosphorylation and inactivation of GAPs." \
"The original PKC-act-raf rate consts are too fast. We lower K1 by 10 X"
call /kinetics/MAPK/craf-1/notes LOAD \
"Couldn't find any ref to the actual conc of craf-1 but I" \
"should try Strom et al Oncogene 5 pp 345" \
"In line with the other kinases in the cascade, I estimate the conc to be" \
"0.2 uM. To init we use 0.15, which is close to equil" \
"16 May 2003: Changing to synaptic levels. Increasing 2.5 fold to 0.5 uM." \
"See Mihaly et al 1991 Brain Res 547(2):309-14" \
"and " \
"Morice et al 1999 Eur J Neurosci 11(6):1995-2006"
call /kinetics/MAPK/MAPKK/notes LOAD \
"Conc is from Seger et al JBC 267:20 pp14373 (1992)" \
"mwt is 45/46 Kd" \
"We assume that phosphorylation on both ser and thr is needed for" \
"activiation. See Kyriakis et al Nature 358 417 1992" \
"Init conc of total is 0.18" \
"Ortiz et al 1995 J Neurosci 15(2):1285-1297 suggest that levels are" \
"higher in hippocampus than other brain regions, and further elevated " \
"in synapses. Estimate 3x higher levels than before, at 0.5 uM." \
"Similar results from Schipper et al 1999 Neuroscience 93(2):585-595" \
"but again lacking in quantitation."
call /kinetics/MAPK/MAPK/notes LOAD \
"conc is from Sanghera et al JBC 265 pp 52 (1990)" \
"A second calculation gives 3.1 uM, from same paper." \
"They est MAPK is 1e-4x total protein, and protein is 15% of cell wt," \
"so MAPK is 1.5e-5g/ml = 0.36uM. which is closer to our first estimate." \
"Lets use this." \
"Updated 16 May 2003." \
"Ortiz et al 1995 J Neurosci 15(2):1285-1297 provide estimates of " \
"ERK2 levels in hippocampus: 1009 ng/mg. This comes to about 3.6uM, which" \
"may still be an underestimate of synaptic levels."
call /kinetics/MAPK/craf-1_star_star/notes LOAD \
"Negative feedback by MAPK_star by hyperphosphorylating craf-1_star gives" \
"rise to this pool." \
"Ueki et al JBC 269(22):15756-15761, 1994" \
""
call /kinetics/MAPK/MAPK-tyr/notes LOAD \
"Haystead et al FEBS Lett. 306(1) pp 17-22 show that phosphorylation" \
"is strictly sequential, first tyr185 then thr183."
call /kinetics/MAPK/MAPKK_star/notes LOAD \
"MAPKK phosphorylates MAPK on both the tyr and thr residues, first" \
"tyr then thr. Refs: Seger et al JBC267:20 pp 14373 1992" \
"The MAPKK itself is phosphorylated on ser as well as thr residues." \
"Let us assume that the ser goes first, and that the sequential phosphorylation" \
"is needed. See Kyriakis et al Nature 358 417-421 1992"
call /kinetics/MAPK/MAPKK_star/MAPKKtyr/notes LOAD \
"The actual MAPKK is 2 forms from Seger et al JBC 267:20 14373(1992)" \
"Vmax = 150nmol/min/mg" \
"From Haystead et al FEBS 306(1):17-22 we get Km=46.6nM for at least one" \
"of the phosphs." \
"Putting these together:" \
"k3=0.15/sec, scale to get k2=0.6." \
"k1=0.75/46.6nM=2.7e-5"
call /kinetics/MAPK/MAPKK_star/MAPKKthr/notes LOAD \
"Rate consts same as for MAPKKtyr."
call /kinetics/MAPK/MAPKK-ser/notes LOAD \
"Intermediately phophorylated, assumed inactive, form of MAPKK"
call /kinetics/MAPK/Raf_star-GTP-Ras/Raf_star-GTP-Ras.1/notes LOAD \
"Kinetics are the same as for the craf-1_star activity, ie.," \
"k1=1.1e-6, k2=.42, k3 =0.105" \
"These are based on Force et al PNAS USA 91 1270-1274 1994." \
"These parms cannot reach the observed 4X stim of MAPK. So lets" \
"increase the affinity, ie, raise k1 10X to 1.1e-5" \
"Lets take it back down to where it was." \
"Back up to 5X: 5.5e-6"
call /kinetics/MAPK/Raf_star-GTP-Ras/Raf_star-GTP-Ras.2/notes LOAD \
"Same kinetics as other c-raf activated forms. See " \
"Force et al PNAS 91 1270-1274 1994." \
"k1 = 1.1e-6, k2 = .42, k3 = 1.05" \
"raise k1 to 5.5e-6" \
""
call /kinetics/MKP-1/notes LOAD \
"MKP-1 dephosphoryates and inactivates MAPK in vivo: Sun et al Cell 75 " \
"487-493 1993. Levels of MKP-1" \
"are regulated, and rise in 1 hour. " \
"Kinetics from Charles et al PNAS 90:5292-5296 1993. They refer" \
"to Charles et al Oncogene 7 187-190 who show that half-life of MKP1/3CH134" \
"is 40 min. 80% deph of MAPK in 20 min" \
"Sep 17 1997: CoInit now 0.4x to 0.0032. See parm searches" \
"from jun96 on."
call /kinetics/MKP-1/MKP1-tyr-deph/notes LOAD \
"The original kinetics have been modified to obey the k2 = 4 * k3 rule," \
"while keeping kcat and Km fixed. As noted in the NOTES, the only constraining" \
"data point is the time course of MAPK dephosphorylation, which this" \
"model satisfies. It would be nice to have more accurate estimates of" \
"rate consts and MKP-1 levels from the literature. " \
"Effective Km : 67 nM" \
"kcat = 1.43 umol/min/mg"
call /kinetics/MKP-1/MKP1-thr-deph/notes LOAD \
"See MKP1-tyr-deph"
call /kinetics/Ras-act-craf/notes LOAD \
"Assume the binding is fast and limited only by the amount of " \
"Ras_star available. So kf=kb/[craf-1]" \
"If kb is 1/sec, then kf = 1/0.2 uM = 1/(0.2 * 6e5) = 8.3e-6" \
"Later: Raise it by 10 X to 4e-5" \
"From Hallberg et al JBC 269:6 3913-3916 1994, 3% of cellular Raf is" \
"complexed with Ras. So we raise kb 4x to 4" \
"This step needed to memb-anchor and activate Raf: Leevers et al Nature" \
"369 411-414" \
"May 16, 2003" \
"Changed Ras and Raf to synaptic levels, an increase of about 2x for each." \
"To maintain the percentage of complexed Raf, reduced the kf by 2.4 fold" \
"to 10." \
""
call /kinetics/PPhosphatase2A/notes LOAD \
"Refs: Pato et al Biochem J 293:35-41(93);" \
"Takai&Mieskes Biochem J 275:233-239" \
"k1=1.46e-4, k2=1000,k3=250. these use" \
"kcat values for calponin. Also, units of kcat may be in min!" \
"revert to Vmax base:" \
"k3=6, k2=25,k1=3.3e-6 or 6,6,1e-6" \
"CoInit assumed 0.1 uM." \
"See NOTES for MAPK_Ras50.g. CoInit now 0.08" \
"Sep 17 1997: Raise CoInt 1.4x to 0.224, see parm" \
"searches from jun 96 on." \
""
call /kinetics/PPhosphatase2A/craf-deph/notes LOAD \
"See parent PPhosphatase2A for parms" \
""
call /kinetics/PPhosphatase2A/MAPKK-deph/notes LOAD \
"See: Kyriakis et al Nature 358 pp 417-421 1992" \
"Ahn et al Curr Op Cell Biol 4:992-999 1992 for this pathway." \
"See parent PPhosphatase2A for parms."
call /kinetics/PPhosphatase2A/craf_star_star-deph/notes LOAD \
"Ueki et al JBC 269(22) pp 15756-15761 1994 show hyperphosphorylation of" \
"craf, so this is there to dephosphorylate it. Identity of phosphatase is not" \
"known to me, but it may be PP2A like the rest, so I have made it so."
call /kinetics/Ras/notes LOAD \
"Ras has now gotten to be a big enough component of the model to" \
"deserve its own group. The main refs are" \
"Boguski and McCormick Nature 366 643-654 '93 Major review" \
"Eccleston et al JBC 268:36 pp 27012-19" \
"Orita et al JBC 268:34 2554246"
call /kinetics/Ras/inact-GEF/notes LOAD \
"Assume that SoS is present only at 50 nM." \
"Revised to 100 nM to get equil to experimentally known levels."
call /kinetics/Ras/GEF_star/notes LOAD \
"phosphorylated and thereby activated form of GEF. See, e.g." \
"Orita et al JBC 268:34 25542-25546 1993, Gulbins et al." \
"It is not clear whether there is major specificity for tyr or ser/thr."
call /kinetics/Ras/GEF_star/GEF_star-act-ras/notes LOAD \
"Kinetics same as GEF-bg-act-ras" \
""
call /kinetics/Ras/GTP-Ras/notes LOAD \
"Only a very small fraction (7% unstim, 15% stim) of ras is GTP-bound." \
"Gibbs et al JBC 265(33) 20437" \
""
call /kinetics/Ras/GDP-Ras/notes LOAD \
"GDP bound form. See Rosen et al Neuron 12 1207-1221 June 1994." \
"the activation loop is based on Boguski and McCormick Nature 366 643-654 93" \
"Assume Ras is present at about the same level as craf-1, 0.2 uM." \
"Hallberg et al JBC 269:6 3913-3916 1994 estimate upto 5-10% of cellular" \
"Raf is assoc with Ras. Given that only 5-10% of Ras is GTP-bound, we" \
"need similar amounts of Ras as Raf."
call /kinetics/Ras/Ras-intrinsic-GTPase/notes LOAD \
"This is extremely slow (1e-4), but it is significant as so little GAP actually" \
"gets complexed with it that the total GTP turnover rises only by" \
"2-3 X (see Gibbs et al, JBC 265(33) 20437-20422) and " \
"Eccleston et al JBC 268(36) 27012-27019" \
"kf = 1e-4" \
""
call /kinetics/Ras/dephosph-GAP/notes LOAD \
"Assume a reasonably good rate for dephosphorylating it, 1/sec"
call /kinetics/Ras/GAP/notes LOAD \
"GTPase-activating proteins. See Boguski and McCormick." \
"Turn off Ras by helping to hydrolyze bound GTP. " \
"This one is probably NF1, ie., Neurofibromin as it is inhibited by AA and lipids," \
"and expressed in neural cells. p120-GAP is also a possible candidate, but" \
"is less regulated. Both may exist at similar levels." \
"See Eccleston et al JBC 268(36) pp27012-19" \
"Level=.002" \
"16 May 2003: Increased level to 0.0036, in line with other concentration" \
"raises at the synapse."
call /kinetics/Ras/GAP/GAP-inact-ras/notes LOAD \
"From Eccleston et al JBC 268(36)pp27012-19 get Kd < 2uM, kcat - 10/sec" \
"From Martin et al Cell 63 843-849 1990 get Kd ~ 250 nM, kcat = 20/min" \
"I will go with the Eccleston figures as there are good error bars (10%). In general" \
"the values are reasonably close." \
"k1 = 1.666e-3/sec, k2 = 1000/sec, k3 = 10/sec (note k3 is rate-limiting)" \
"5 Nov 2002: Changed ratio term to 4 from 100. Now we have" \
"k1=8.25e-5; k2=40, k3=10. k3 is still rate-limiting."
call /kinetics/Ras/CaM-bind-GEF/notes LOAD \
"We have no numbers for this. It is probably between" \
"the two extremes represented by the CaMKII phosph states," \
"and I have used guesses based on this." \
"kf=1e-4" \
"kb=1" \
"The reaction is based on Farnsworth et al Nature 376 524-527" \
"1995"
call /kinetics/Ras/CaM-GEF/notes LOAD \
"See Farnsworth et al Nature 376 524-527 1995"
call /kinetics/Ras/CaM-GEF/CaM-GEF-act-ras/notes LOAD \
"Kinetics same as GEF-bg_act-ras" \
""
call /kinetics/Sos/Shc_bind_Sos.Grb2/notes LOAD \
"Sasaoka et al JBC 269:51 pp 32621 1994, table on pg" \
"32623 indicates that this pathway accounts for about " \
"50% of the GEF activation. (88% - 39%). Error is large," \
"about 20%. Fig 1 is most useful in constraining rates." \
"" \
"Chook et al JBC 271:48 pp 30472, 1996 say that the Kd is" \
"0.2 uM for Shc binding to EGFR. The Kd for Grb direct binding" \
"is 0.7, so we'll ignore it."
call /kinetics/Sos/Grb2_bind_Sos_star/notes LOAD \
"Same rates as Grb2_bind_Sos: Porfiri and McCormick JBC" \
"271:10 pp 5871 1996 show that the binding is not affected" \
"by the phosph."
call /kinetics/Sos/dephosph_Sos/notes LOAD \
"The only clue I have to these rates is from the time" \
"courses of the EGF activation, which is around 1 to 5 min." \
"The dephosph would be expected to be of the same order," \
"perhaps a bit longer. Lets use 0.002 which is about 8 min." \
"Sep 17: The transient activation curve matches better with" \
"kf = 0.001"
call /kinetics/Sos/Grb2_bind_Sos/notes LOAD \
"As there are 2 SH3 domains, this reaction could be 2nd order." \
"I have a Kd of 22 uM from peptide binding (Lemmon et al " \
"JBC 269:50 pg 31653). However, Chook et al JBC 271:48 pg30472" \
"say it is 0.4uM with purified proteins, so we believe them." \
"They say it is 1:1 binding."
call /kinetics/Sos/Sos/notes LOAD \
"I have tried using low (0.02 uM) initial concs, but these" \
"give a very flat response to EGF stim although the overall" \
"activation of Ras is not too bad. I am reverting to 0.1 " \
"because we expect a sharp initial response, followed by" \
"a decline." \
"Sep 17 1997: The transient activation curve looks better with" \
"[Sos] = 0.05." \
"Apr 26 1998: Some error there, it is better where it was" \
"at 0.1"
call /kinetics/43Scomplex/notes LOAD \
"40S_complex consist of Quaternary complex, mRNA complex, " \
"40S Ribosomes."
call /kinetics/PKC/PKC-act-by-Ca/notes LOAD \
"Need est of rate of assoc of Ca and PKC. Assume it is fast" \
"The original parameter-searched kf of 439.4 has been" \
"scaled by 1/6e8 to account for change of units to n. Kf now 8.16e-7, kb=.6085" \
"Raised kf to 1e-6 to match Ca curve, kb to .5" \
""
call /kinetics/PKC/PKC-act-by-DAG/notes LOAD \
"Need est of rate. Assume it is fast" \
"Obtained from param search" \
"kf raised 10 X : see Shinomura et al PNAS 88 5149-5153 1991." \
"kf changed from 3.865e-7 to 2.0e-7 in line with closer analysis of" \
"Shinomura data." \
"26 June 1996: Corrected DAG data: reduce kf 15x from " \
"2e-7 to 1.333e-8"
call /kinetics/PKC/PKC-DAG-to-memb/notes LOAD \
"Raise kb from .087 to 0.1 to match data from Shinomura et al." \
"Lower kf from 1.155 to 1.0 to match data from Shinomura et al."
call /kinetics/PKC/PKC-act-by-Ca-AA/notes LOAD \
"Schaechter and Benowitz We have to increase Kf for conc scaling" \
"Changed kf to 2e-9 on Sept 19, 94. This gives better match." \
""
call /kinetics/PKC/PKC-act-by-DAG-AA/notes LOAD \
"Assume slowish too. Schaechter and Benowitz"
call /kinetics/PKC/PKC-basal-act/notes LOAD \
"Initial basal levels were set by kf = 1, kb = 20. In model, though, the" \
"basal levels of PKC activity are higher."
call /kinetics/PKC/PKC-act-by-AA/notes LOAD \
"Raise kf from 1.667e-10 to 2e-10 to get better match to data."
call /kinetics/PKC/PKC-n-DAG/notes LOAD \
"kf raised 10 X based on Shinomura et al PNAS 88 5149-5153 1991" \
"closer analysis of Shinomura et al: kf now 1e-8 (was 1.66e-8)." \
"Further tweak. To get sufficient AA synergy, increase kf to 1.5e-8" \
"26 June 1996: Corrected DAG levels: reduce kf by 15x from" \
"1.5e-8 to 1e-9"
call /kinetics/PKC/PKC-DAG/notes LOAD \
"CoInit was .0624" \
""
call /kinetics/PKC/PKC-n-DAG-AA/notes LOAD \
"Reduced kf to 0.66X to match Shinomura et al data." \
"Initial: kf = 3.3333e-9" \
"New: 2e-9" \
"Newer: 2e-8" \
"kb was 0.2" \
"now 2."
call /kinetics/PKC/PKC-cytosolic/notes LOAD \
"Marquez et al J. Immun 149,2560(92) est 1e6/cell for chromaffin cells" \
"We will use 1 uM as our initial concen" \
""
call /kinetics/DAG/notes LOAD \
"The conc of this has been a problem. Schaecter and Benowitz use 50 uM," \
"but Shinomura et al have < 5. So I have altered the DAG-dependent " \
"rates in the PKC model to reflect this."
call /kinetics/Basal_Translation/notes LOAD \
"It will contribute to mTOR independent translation."
call /kinetics/doqcsinfo/notes LOAD \
"This model consists of various sub-modules. They are as follows:" \
"1) BDNF receptor signaling 2) AKT signaling 3) 4E-BP model 4) S6 Kinase model" \
"5) CaMKIII model 6) Protein synthesis model 7) CaM 8) PKC 9) MAPK model. "
complete_loading