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Ajay_Bhalla_
2004_Feedback_
Tuning
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Ajay_Bhalla_
2004_Feedback_
Tuning
PKC
 Molecule
 Reaction
PLA2
PLCbeta
Gq
MAPK
Ras
EGFR
Sos
PLC_g
CaMKII
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PP1
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PKA
AC

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Reaction List for pathway PKC (Pathway Number 348)

Kd is calculated only for second order reactions, like nA+nB <->nC or nA<->nC+nD, where n is number and A,B,C,D are molecules, where as for first order reactions Keq is calculated. Kd for higher order reactions is not considered.
  Name KfKbKdtauSubstrateProduct
1 PKC-act-by-AA0.0001
(uM^-1 s^-1)
0.1
(s^-1)
Kd(bf) = 833.3542(uM)-AA
PKC-cytosolic
PKC-AA*
  Raise kf from 1.667e-10 to 2e-10 to get better match to data.
2 PKC-act-by-Ca0.6
(uM^-1 s^-1)
0.5
(s^-1)
Kd(bf) = 0.8333(uM)-PKC-cytosolic
Ca
PKC-Ca
  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
3 PKC-act-by-Ca-AA0.0012
(uM^-1 s^-1)
0.1
(s^-1)
Kd(bf) = 83.3354(uM)-PKC-Ca
AA
PKC-Ca-AA*
  Schaechter and Benowitz We have to increase Kf for conc scaling Changed kf to 2e-9 on Sept 19, 94. This gives better match.
4 PKC-act-by-DAG0.008
(uM^-1 s^-1)
8.6348
(s^-1)
Kd(bf) = 1079.3729(uM)-DAG
PKC-Ca
PKC-Ca-DAG
  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
5 PKC-act-by-DAG-A
A
2
(s^-1)
0.2
(s^-1)
Keq = 0.1(uM)0.455secPKC-DAG-AA
PKC-DAG-AA*
  Assume slowish too. Schaechter and Benowitz
6 PKC-basal-act1
(s^-1)
50
(s^-1)
Keq = 50(uM)0.02secPKC-cytosolic
PKC-basal*
  Initial basal levels were set by kf = 1, kb = 20. In model, though, the basal levels of PKC activity are higher.
7 PKC-Ca-to-memb1.2705
(s^-1)
3.5026
(s^-1)
Keq = 2.7569(uM)0.21secPKC-Ca
PKC-Ca-memb*
8 PKC-DAG-to-memb1
(s^-1)
0.1
(s^-1)
Keq = 0.1(uM)0.909secPKC-Ca-DAG
PKC-DAG-memb*
  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.
9 PKC-n-DAG0.0006
(uM^-1 s^-1)
0.1
(s^-1)
Kd(bf) = 166.6658(uM)-PKC-cytosolic
DAG
PKC-DAG
  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
10 PKC-n-DAG-AA0.018
(uM^-1 s^-1)
2
(s^-1)
Kd(bf) = 111.1111(uM)-PKC-DAG
AA
PKC-DAG-AA
  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.


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