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Parameter Value Reference

k1 0.01 Estimate

k2 0.002 Estimate

k3 0.001 Estimate

k4 0.3 Estimate

KM4 78 Estimate

V5 46.2 Estimate

KM5 117 Estimate

k6 0.05 Estimate

KM6 6170 Estimate

k7 5.5 Estimate

KM7 80.9 Estimate

k8 0.045 Estimate

k9 0.089 Estimate

k10 20 Estimate

KM10 80000 [BCC+00]

k11 0.037 Estimate

KM11 8800 Estimate

k12 20 Estimate

KM12 80000 [BCC+00]

k13 0.04 Estimate

KM13 48000 Estimate

k14 0.163 Estimate

KM14 48000 Estimate

k15 50 Estimate

KM15 20000 Estimate

V16 15000 Estimate

KM16 7260 Estimate

k17 0.09 Estimate

KM17 50 Estimate

k18 0.183 Estimate

KM18 500 Estimate

V19 78 Estimate

KM19 30 Estimate

k20 0.1 Estimate

KM20 13.2 Estimate

k21 5.6 Estimate

KM21 7200 Estimate

k22 0.04 Estimate

KM22 2600 Estimate

k23 0.45 Estimate

KM23 1250 Estimate

k24 5.17 Estimate

KM24 24500 Estimate

k25 0.05 Estimate

KM25 2150 Estimate

k26 0.4 Estimate

KM26 4316 Estimate

k27 0.089 Estimate

KM27 52000 Estimate

k28 30 Estimate

KM28 160 Estimate

k29 0.0308 Estimate

KM29 55000 Estimate

k30 32 Estimate

KM30 60 Estimate

k31 0.0017 Estimate

KM31 97.6 Estimate

k32 0.76 Estimate

KM32 181 Estimate

V33 468 Estimate

KM33 2.8 Estimate

k34 0.798 Estimate

KM34 10 Estimate

k35 0.04 Estimate

KM35 30000 Estimate

V36 821 Estimate

KM36 43300 Estimate

k37 0.397 Estimate

KM37 20700 Estimate

k38 0.04 Estimate

KM38 30000 Estimate

V39 821 Estimate

KM39 43300 Estimate

k40 0.0659 Estimate

KM40 42000 Estimate

k41 0.0148 Estimate

k42 0.0561 Estimate

k43 0.0624 Estimate

k44 0.002 [HCC+05]

k45 0.02 [HCC+05]

k46 0.00038 Estimate

k47 0.0155 Estimate

k48 0.14 Estimate

KM48 482 Estimate

V49 83000 Estimate

KM49 29100 Estimate

k50 0.0007 Estimate

k51 0.98 Estimate

Place Reference

Concentration

R 80 Estimate

PI3K 100 [MJ+04]

PIP2 7000 [CAZ04]

PTEN 0.1 Estimate

AKT 200 [BDF+05]

PDK1 1000 Estimate

PDK2 3 Estimate

PP2A 150 [KFK+03]

RAS 18900 [SEG+02]

RAF 66.4 [SEG+02]

MEK 36500 [SEG+02]

ERK 34900 [SEG+02]

MKP3 2.4 Estimate

P90RSK 5 [BF00]

BCL2 100 Estimate

BAD 100 Estimate

BAX 100 [JXD+98]

NOX5 2000 Estimate

ROS 200 Estimate

PAK 500 [LNL+04]



Note:

Assumed cell volume : 1 x 10^-12 L (from [SEG+02] where cell diameter is 15uM)

For Ras, Raf, MEK and ERK, the numbers given are in number of molecules

Ras 1.14 x 10^7 molecules

Raf 4 x 10^4 molecules

MEK 2.2 x 10^7 molecules

ERK 2.1 x 10^7 molecules

6.022 x

Avogadro constant:10^23

Thus, Ras = (1.14 x 10^7 / 6.022 x 10^23 ) / 1 x 10^-12 = 18900 nM

Same for Raf, MEK and ERK

References

[MJY+04]

[CAZ04]

[BDF+05]

[KFK+03]

[SEG+02]

[BF00]

[JXD+98]

[LNL+04]

[BCC+00]

[HCC+05]

References

Lan Ma, Chris Janetopoulos, Liu Yang, Peter N. Devreotes, and Pablo A Iglesias, "Two Complementary, Local Excitation, Glob

D. Chodniewicz, A. M. Alterai¯, and D. V. Zhelev. Experimental Evidence for the Limiting Role of Enzymatic Reactions in Chem

S. F. Barnett, D. Defeo-Jones, S. Fu, P. J. Hancock, K. M. Haskell, R. E. Jones, J. A. Kahana, A. M. Kral, K. Leander, L. L. Lee

S. Kikuchi, K. Fujimoto, N. Kitagawa, T. Fuchikawa, M. Abe, K. Oka, K. Takei, and M. Tomita. Kinetic simulation of signal trans

B. Schoeberl, C. Eichler-Jonsson, E. D. Gilles, and G. MÄuller. Computational modeling of the dynamics of the MAP kinase cas

R. R. Bhatt and J. E. F. Jr. Cloning and Characterization of Xenopus Rsk2, the Predominant p90 Rsk Isozyme in Oocytes and E

J. M. JÄurgensmeier, Z. Xie, Q. Deveraux, L. Ellerby, D. Bredesen, and J. C. Reed. Bax directly induces release of cytochrome

T.-H. Loo, Y.-W. Ng, L. Lim, and E. Manser. GIT1 Activates p21-Activated Kinase through a Mechanism Independent of p21 Bi

Ricardo M Biondi, Peter CF Cheung, Antonio Casamayor, Maria Deak, Richard A Currie and Dario R Alessi, "Identification of a

F. Hua, M. G. Cornejo, M. H. Cardone, C. L. Stokes, and D. A. Lau®enburger. Effects of bcl-2 levels on fas signaling-induced c

ry, Local Excitation, Global Inhibition Mechanisms Acting in Parallel Can Explain the Chemoattractant-Induced Regulation of PI(3,4,5)P3 Re

matic Reactions in Chemoattractant-induced Pseudopod Extension in Human Neutrophils. J Biol Chem, 279(23):24460-24466, 2004.

Kral, K. Leander, L. L. Lee, J. Malinowski, E. M. McAvoy, D. D. Nahas, R. G. Robinson, and H. E. Huber. Identifcation and Characterization o

simulation of signal transduction system in hippocampal longterm potentiation with dynamic modeling of protein phosphatase 2A. Neural Ne

ics of the MAP kinase cascade activated by surface and internalized EGF receptors. Nature Biotechnology, 20(4):370-375, 2002.

Isozyme in Oocytes and Eggs. J Biol Chem, 275(42):32983-32990, 2000.

es release of cytochrome c from isolated mitochondria. Cell Biology, 95(9):4997{5002,1998.

sm Independent of p21 Binding. Molecular and Cell Biology, 24(9):3849{3859, May 2004.

Alessi, "Identification of a pocket in the PDK1 kinase domain that interacts with PIF and the C-terminal residues of PKA", The EMBO journal

on fas signaling-induced caspase-3 activation: Molecular genetic tests of computational model predictions. Journal of Immunology, 175:985-9

nduced Regulation of PI(3,4,5)P3 Response in Dictyostelium Cells", Biophysical Journal, Vol 87, Dec 2004

, 279(23):24460-24466, 2004.

Identifcation and Characterization of Pleckstrin Homology Domain Dependent and Isozyme Speci¯c Akt Inhibitors. Biochem J, 385:399-408

protein phosphatase 2A. Neural Networks, 16(9):1389-1398, 2003.

ogy, 20(4):370-375, 2002.







esidues of PKA", The EMBO journal Vol 19 No 5 pp 979-988, 2000

ns. Journal of Immunology, 175:985-995, 2005.

t Inhibitors. Biochem J, 385:399-408, 2005.



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