Simulation parameters

Reaction units

Reaction rate units are in number of reactant molecules and seconds, i.e. 1/sec for zeroth order, 1/(#.sec) for first order, and so on. This formulation is independent of volume terms and is therefore appropriate when considering interactions between compartments with different volumes. The default volume for compartments in the signaling model is 1e-15 m^3, that is, a cube of side 10 microns.

Enzyme units

Enzyme Km is in microMolar and Vmax in 1/sec.

Concentration units.

Concentrations are in microMolar. In the case of membrane-bound molecules the volume calculations assume normal cellular ratios of membrane to cytosol.

Simulation parameters: EGFR

Reaction A: EGFR and SoS
References
Figure Reac # kf kb
A 1 0.000007 0.25
A 2 0.002 0.00033
A 4 0.0016667 0
A 5 4.1667E-08 0.0168
A 6 8.333E-07 0.1
A 8 0.001 0
A 10 4.1667E-08 0.0168
Enzymes A: EGF and EGFR
References
Figure Enz # Km Vmax
A 3 0.833333333 0.2
A 7 0.50505 0.02
A 9 2.564166667 10
Concs A: EGFR
References
Figure Name Conc
A EGFR 0.16667
A SHC 0.5
A Grb2 1
A SoS 0.1

    A: EGFR:

  1. S. H. Ryu, K. S. Cho, K.-Y Lee, P.-G. Suh, S. G. Rhee, J. Biol. Chem. 262, 12511 (1987)
  2. S. Okada, K. Yamauchi, J. E. Pessin, J. Biol. Chem. 270, 20737 (1995)
  3. K. K. Teng et al., J. Biol. Chem. 270, 20677 (1995)
  4. S. B. Waters et al., J. Biol. Chem. 271, 18224 (1996)
  5. K. Helin and L. Beguinot, J. Biol. Chem. 266, 8363 (1991)
  6. Grb2/Sos interaction: Y. M. Chook, G. D. Gish, C. M. Kay, E. F. Pai, T. Pawson, J. Biol. Chem. 271, 30472 (1996).

Simulation parameters: Ras activation

Reaction B: Ras activation
References
Figure Reac # kf kb
B 2 1 0
B 4 0.1 0
B 5 0.0001 1
B 7 1 0
B 8 0.00001 1
B 12 0.0001 0
Enzymes B: Ras activation
References
Figure Enz # Km Vmax
B 1 7.5 9
B 3 3.333333333 4
B 6 3.333333333 4
B 9 0.50505 0.02
B 10 0.50505 0.02
B 11 0.50505 0.02
B 13 1.0104 10
Concs B: Ras
References
Figure Name Conc
B inact_GEF 0.1
B GAP 0.002
B GDP_Ras 0.2

    B: Ras:

  1. CaM activation of Ras: C. L. Farnsworth et al., Nature 376, 524 (1995)
  2. PKC activation of Ras: S. Orita et al., J. Biol. Chem. 268, 25542 (1993)
  3. PKC activation of Ras: W. Kolch et al., Nature 364, 249 (1993)
  4. E. Gulbins et al., Mol. Cell Biol. 14, 906 (1994)
  5. bg activation: M. S. Boguski and F. McCormick, Nature 366, 643 (1993),
  6. H. Daub, F. Ullrich Weiss, C. Wallasch, A. Ullrich, Nature 379, 557 (1996)
  7. EGF activation: T. Sasaoka, W. J. Langlois, J. W. Leitner, B. Draznin, J. M. Olefsky, J. Biol. Chem. 269, 32621 (1994)
  8. PKA inactivation: P. L. Hordijk, I. Verlaan, K. Jalink, E. J. van Corven, W. H. Moolenaar, J. Biol. Chem. 269, 3534 (1994)
  9. B. M. T. Burgering, G. J. Pronk, P. C. van Weeren, P. Chardin, J. L. Bos, EMBO J. 12, 4211 (1993)

Simulation parameters: Adenylyl Cyclases 1/8 and 2

Reaction C: Adenylyl Cyclases 1/8 and 2
References
Figure Reac # kf kb
C 1 0.00021 1
C 3 0.000083333 1
C 5 0.00083333 1
C 7 0.1 0
C 10 0.0013888 1
C 13 0.1 0
C 16 0.0012 5
Enzymes C: Adenylyl Cyclases 1/8 and 2
References
Figure Enz # Km Vmax
C 2 20 18
C 4 20 18
C 6 20 18
C 8 33.33333333 4
C 9 20.115 7
C 11 60 54
C 12 7.5 9
C 14 19.84166667 10
C 15 19.84166667 20
C 17 40 1.667
C 18 40 10
Concs C: Adenylyl Cyclases 1/8 and 2
References
Figure Name Conc
C ATP 5000
C AC1 0.02
C AC2 0.015
C cAMP_PDE 0.45
C PDE1 2

    C: AC 1/8, AC2:

  1. J. P. Pieroni, O. Jacobowitz, J. Chen, R. Iyengar, Curr. Opin. Neurobiol. 3, 345 (1993)
  2. O. Jacobowitz, J. Chen, R. T. Premont, R. Iyengar, J. Biol. Chem. 268, 3829 (1993)
  3. W.-J. Tang, J. Krupinski, A. G. Gilman, J. Biol. Chem. 266, 8595 (1991)
  4. M. Yoshimura and D. M. F. Cooper, J. Biol. Chem. 268, 4604 (1993)
  5. K. D. Lustig, B. R. Conklin, P. Herzmark, R. Taussig, H. R. Bourne, J. Biol. Chem. 268, 13900 (1993)
  6. PKA stimulation of PDE: C. Sette, E. Vicini, M. Conti, J. Biol. Chem. 269, 18271 (1994).

Simulation parameters: mGluR and Gq

Reaction D: mGluR and Gq
References
Figure Reac # kf kb
D 1 500 1000
D 2 0.000028 0.1
D 3 0.000028 10
D 4 0.000001 1
D 5 0.00000001 0.0001
D 6 0.01 0
D 7 0.0133 0
D 8 0.00001 0
D 9 0.0001 0
Concs D: mGluR and Gq
References
Figure Name Conc
D G_GDP 1
D mGluR 0.3

    D: mGluR/Gq Gq:

  1. S. P. Fay, R. G. Posner, W. N. Swann, L. A. Sklar, Biochem. 30, 5066 (1991)
  2. I.-H. Pang and P. Sternweis, J. Biol. Chem. 265, 18707 (1990)
  3. mGluR: M. Martin, J. M. Sanz, A. Cubero, FEBS Lett 316, 191 (1993)
  4. K. Nakamura, T. Nukada, T. Haga, H. Sugiyama, J. Physiol. Lond. 474, 35 (1994)
  5. combined: Berstein et al., J. Biol. Chem. 267, 8081 (1992).

Simulation parameters: PLA2 and AA

Reaction E: PLA2 and AA
References
Figure Reac # kf kb
E 1 0.000000002 0.5
E 3 1.6667E-06 0.1
E 5 0.00000002 0.1
E 7 0.000000005 4
E 10 0.17 0
E 11 0.00001 0.1
E 13 0.4 0
Enzymes E: PLA2
References
Figure Enz # Km Vmax
E 2 20 11.04
E 4 20 5.4
E 6 20 36
E 8 20 60
E 9 25.64166667 20
E 12 20 120
Concs E: PLA2
References
Figure Name Conc
E PIP2* 2.5
E PLA2_cyt 0.4
E APC 30

    E: PLA2:

  1. MAPK activation: R. A. Nemenoff et al., J. Biol. Chem. 268, 1960 (1993)
  2. J. Wijkander and R.Sundler, Eur. J. Biochem. 202, 873 (1991)
  3. C. C. Leslie and J. Y. Channon, Biochim. Biophys. Acta 1045, 261 (1990)
  4. L.-L. Lin et al., Cell 72, 269 (1993)
  5. C. C. Leslie, J. Biol. Chem. 266, 11366 (1991).

Simulation parameters: PLC-gamma

Reaction F: PLC-gamma
References
Figure Reac # kf kb
F 1 0.0003 10
F 3 0.05 0
F 5 0.00002 10
Enzymes F: PLC-gamma
References
Figure Enz # Km Vmax
F 2 97 14
F 4 0.333333333 0.2
F 6 19.79166667 57
Concs F: PLC_gamma
References
Figure Name Conc
F PLC_g 0.82
F PIP2 10

    F: PLCg:

  1. M. I. Wahl, G. A. Jones, S. Nishibe, S. G. Rhee, G. Carpenter, J. Biol. Chem. 267, 10447 (1992)
  2. S. Nishibe et al., Science 250, 1253 (1990)
  3. C.-Y. J. Hsu, D. R. Hurwitz, M. Mervic, A. Zilberstein, J. Biol. Chem. 266, 603 (1991)
  4. S. H. Ryu, K. S. Cho, K.-Y. Lee, P.-G Suh, S. G. Rhee, J. Biol. Chem. 262, 12511 (1987).

Simulation parameters: PLC-beta

Reaction G: PLC-beta
References
Figure Reac # kf kb
G 1 0.000005 1
G 2 0.0000042 1
G 3 0.00005 1
G 4 0.000042 1
G 5 0.0133 0
G 8 0.15 0
G 9 2.5 0
Enzymes G: PLC-beta
References
Figure Enz # Km Vmax
G 6 5 48
G 7 19.84166667 10
Concs G: PLC_beta
References
Figure Name Conc
G PIP2 10
G PLC 0.8

    G: PLCb:

  1. S. H. Ryu, K. S. Cho, K.-Y. Lee, P.-G Suh, S. G. Rhee, J. Biol. Chem. 262, 12511 (1987)
  2. A. V. Smrcka, J. R. Hepler, K. O. Brown, P. C. Sternweis, Science 251, 804 (1991)
  3. P. C. Sternweis, A. V. Smrcka, S. Gutowski, Phil. Trans. R. Soc. Lond. B. 336:1276, 35-41 (1992).

Simulation parameters: MAPK cascade

Reaction H: MAPK cascade
References
Figure Reac # kf kb
H 5 0.00004 0.5
Enzymes H: MAPK cascade
References
Figure Enz # Km Vmax
H 1 66.66666667 4
H 2 25.64166667 10
H 3 15.6565 6
H 4 15.6565 6
H 6 0.159091667 0.105
H 7 0.159091667 0.105
H 8 15.6565 6
H 9 15.6565 6
H 10 0.046296667 0.15
H 11 0.046296667 0.15
H 12 0.066666667 1
H 13 0.066666667 1
Concs H: MAPK cascade
References
Figure Name Conc
H MKP1 0.0032
H PP2A 0.224
H craf_1 0.2
H MAPKK 0.18
H MAPK 0.36

    H: MAPK:

  1. Ras activation by PKC: W. Kolch et al., Nature 364, 249 (1993)
  2. MAPKK activation by Ras: J. M. Kyriakis et al., Nature 358, 417 (1992)
  3. MAPKK activation by Ras: T. Force et al., Proc. Natl. Acat. Sci. U.S.A. 91, 1270 (1994)
  4. MAPK: R. Seger et al., J. Biol. Chem. 267, 14373 (1992)
  5. MAPK: T. A. J. Haystead, P. Dent, J. Wu, C. M. M. Haystead, T. W. Sturgill, FEBS Lett. 306, 17 (1992)
  6. MAPK: J. S. Sanghera, H. B. Paddon, S. A. Bader, S. L. Pelech, J. Biol. Chem. 265, 52 (1990)
  7. Combined: C.-Y. F. Huang, J. E. Ferrell, Jr., Proc. Natl. Acad. Sci. U.S.A. 93, 10078 (1996).

Simulation parameters: CaMKII

Reaction I: CaMKII
References
Figure Reac # kf kb
I 1 0.000083333 5
I 7 0.001667 0.1
I 9 0.003 0
Enzymes I: CaMKII
References
Figure Enz # Km Vmax
I 2 1.62 0.5
I 3 1.62 0.5
I 4 2.5 0.5
I 5 2.5 0.5
I 6 5.1 0.35
I 8 5.1 0.35
I 10 1.62 6
I 11 1.62 6
I 12 2.5 6
I 13 2.5 6
I 14 5.099 0.35
I 15 5.099 0.35
I 16 5.099 0.35
Concs I: CaMKII
References
Figure Name Conc
I CaMKII 70

    I: CaMKII:

  1. P. I. Hanson, T. Meyer, L. Stryer, H. Schulman, Neuron 12, 943 (1994)
  2. P. I. Hanson and H. Schulman, Ann. Rev. Biochem. 61, 559 (1992)
  3. P. I. Hanson and H. Schulman, J. Biol. Chem. 267, 17216 (1992)
  4. S. G. Miller and M. B. Kennedy, Cell 44, 861 (1986)
  5. J. E. Lisman, Trends Neurosci. 17, 406 (1994)
  6. J. E. Lisman and M. A. Goldring, Proc. Natl. Acad. Sci. U.S.A. 85, 5320 (1988).

Simulation parameters: PKA

Reaction J: PKA
References
Figure Reac # kf kb
J 1 0.00009 33
J 2 0.00009 33
J 3 0.000125 110
J 4 0.000125 32.5
J 5 60 0.00003
J 6 60 0.00003
J 7 0.0001 1
Concs J: PKA
References
Figure Name Conc
J R2C2 0.5
J PKA_inhibitor 0.25

    J: PKA:

  1. S. O. Doskeland and D. Ogreid, J. Biol. Chem. 259, 2291 (1984)
  2. S. O. Doskeland and D. Ogreid, Int. J. Biochem. 13, 1 (1981)
  3. P. Hasler, J. J. Moore, G. M. Kammer, FASEB J. 6, 2735 (1992)
  4. S. B. Smith, H. D. White, J. B. Siegel, E. G. Krebs, , Proc. Natl. Acad. Sci. U.S.A. 78, 1591 (1981).

Simulation parameters: PKC

Reaction K: PKC
References
Figure Reac # kf kb
K 1 1 50
K 2 2E-10 0.1
K 3 1.2705 3.5026
K 4 0.000000002 0.1
K 5 1 0.1
K 6 2 0.2
K 7 0.000001 0.5
K 8 1.3333E-08 8.6348
K 9 0.000000001 0.1
K 10 0.00000003 2
Concs K: PKC
References
Figure Name Conc
K PKC_inactive 1

    K: PKC:

  1. Review: Y. Nishizuka, Nature 334, 661 (1988)
  2. J. D. Schaechter and L. I. Benowitz, J. Neurosci. 13, 4361 (1993)
  3. T. Shinomura, Y. Asaoka, M. Oka, K. Yoshida, Y. Nishizuka, Proc. Natl. Acad. Sci. U.S.A. 88, 5149 (1991)
  4. U. Kikkawa, Y. Takai, R. Minakuchi, S. Inohara, Y. Nishizuka, J. Biol. Chem. 257, 13341 (1982).

Simulation parameters: Calcium regulation

Reaction L: Calcium regulation
References
Figure Reac # kf kb
L 6 25 0
L 7 0.00000001 144
L 8 1.2E-11 1
L 9 1E-20 1
Enzymes L: Ca pump
References
Figure Enz # Km Vmax
L 1 0.2 72
Concs L: Ca regulation
References
Figure Name Conc
L Ca 0.08
L Ca_stores 6.3328
L Stores_Leak 0.001
L Ca_transp 0.0083838
L IP3R 0.016643
L Ca_pump 0.00083333
L Ca_ext 4000
L Extracell_Leak 0.00083333
L Cap_channel 0.00083333

Channel Permeabilities

Permeability
References
Figure Channel Permeability
L 2 0.004
L 3 8
L 4 0.005
L 5 19.2

    L: Ca:

  1. R. N. McBurney and I. R. Neering Trends Neurosci. 10, 164 (1987)
  2. T. Meyer and L. Stryer, Proc. Natl. Acad. Sci. U.S.A. 85, 5051 (1988)
  3. D. A. Lauffenburger and J. J. Linderman, Receptors: models for binding, trafficking and signaling. (Oxford University Press, New York, 1993).

Simulation parameters: CaM

Reaction M: CaM
References
Figure Reac # kf kb
M 1 2E-10 72
M 2 0.000006 10
M 3 0.000000775 10
M 4 0.0000005 1
M 6 0.005 0
Enzymes M: CaM
References
Figure Enz # Km Vmax
M 5 10.012 0.67
M 7 28.62666667 0.58
M 8 28.595 0.35
Concs M: CaM
References
Figure Name Conc
M CaM 20
M neurogranin 10

    M: CaM:

  1. W. Drabikowski, H. Brzeska, S. Yu. Venyaminov, J. Biol. Chem. 257, 11584 (1982)
  2. T. Meyer, P. I. Hanson, L. Stryer, H. Schulman, Science 256, 1199 (1992)
  3. S. Forsen, H. J. Vogel, T. Drakenberg, Calcium and cell function VI, 113 (1986)
  4. P. Stemmer and C. B. Klee, Biochemistry 33, 6859 (1994)
  5. J. R. Slemmon and M. R. Martzen, J. Neurochem. 64, 92 (1995)
  6. K.-P. Huang, F. L. Huang, H.-C. Chen, Arch. Biochem. Biophys. 305, 570 (1993).

Simulation parameters: CaN/PP2B (Calcineurin)

Reaction N: CaN/PP2B (Calcineurin)
References
Figure Reac # kf kb
N 1 2.78E-08 1
N 2 1E-11 1
N 3 0.001 1
N 4 0.00000373 1
N 5 0.0000004 1
Concs N: Calcineurin/PP2B
References
Figure Name Conc
N Calcineurin 1

    N: Calcineurin (CaN, PP2B):

  1. P. Stemmer and C. B. Klee, Biochem. 33, 6859 (1994)
  2. M. C. Mumby and G. Walter, Physiol. Rev. 73, 673 (1993)
  3. B. A. Perrino et al., J. Biol. Chem. 267, 15965 (1992)
  4. K. Seki, H.-C. Chen, K.-P. Huang, Arch. Biochem. Biophys. 316, 673 (1995).

Simulation parameters: PP1

Reaction O: PP1
References
Figure Reac # kf kb
O 2 0.0008333 0.1
O 3 1 0
Enzymes O: PP1
References
Figure Enz # Km Vmax
O 1 7.828333333 6
O 4 4.970833333 0.34
O 5 4.970833333 0.34
O 6 7.828333333 6
O 7 7.5 9
O 8 4.97 0.034
Concs O: PP1
References
Figure Name Conc
O PP1_active 1.8
O PP2A 0.12
O I1 1.8

    O: PP1:

  1. J. Lisman, Trends Neurosci. 17, 406 (1994)
  2. P. Cohen, Ann. Rev. Bioch. 58, 453 (1989)
  3. P. Stralfors, Eur. J. Biochem. 149, 295 (1985)
  4. Y. Saitoh, H. Yamamoto, K. Fukunaga, Y. Matsukado, E. Miyamoto, J. Neuroch. 49, 1286 (1987)
  5. J. G. Foulkes, S. J. Strada, P. J. F. Henderson, P. Cohen, Eur. J. Biochem. 132, 309 (1983).

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