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Accession Type:
Network
MAPK_network_
2003
Shared_Object_
MAPK_network_
2003
PKC
PLA2
PLCbeta
Gq
MAPK
Ras
EGFR
Sos
PLC_g
CaMKII
CaM
 Molecule
 Reaction
PP1
PP2B
PKA
AC

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Reaction List for pathway CaM (Pathway Number 217)

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 CaM-Ca3-bind-Cakf
(uM^-1 s^-1)
10
(s^-1)
Kd(bf) = 21.5054(uM)-CaM-Ca3
Ca
CaM-Ca4
  Use K3 = 21.5 uM here from Stemmer and Klee table 3. kb/kf =21.5 * 6e5 so kf = 7.75e-7, kb = 10
2 CaM-TR2-bind-Cakf
(uM^-2 s^-1)
72
(s^-1)
Kd(af) = 1(uM)-CaM
Ca
Ca
CaM-TR2-Ca2
  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 !)....
3 CaM-TR2-Ca2-bind
-Ca
kf
(uM^-1 s^-1)
10
(s^-1)
Kd(bf) = 2.7778(uM)-CaM-TR2-Ca2
Ca
CaM-Ca3
  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
4 dephosph-neurogr
anin
kf
(s^-1)
0
(s^-1)
--neurogranin*
neurogranin
  This is put in to keep the basal levels of neurogranin* experimentally reasonable. From various papers, specially Ramakers et al JBC 270:23 1995 13892-13898, it looks like the basal level of phosph is between 20 and 40%. I est around 25 % The kf of 0.005 gives around this level at basal PKC activity levels of 0.1 uM active PKC.
5 neurogranin-bind
-CaM
kf
(uM^-1 s^-1)
1
(s^-1)
Kd(bf) = 3.3333(uM)-neurogranin
CaM
neurogranin-CaM
  Surprisingly, no direct info on rates from neurogranin at this time. These rates are based on GAP-43 binding studies. As GAP-43 and neurogranin share near identity in the CaM/PKC binding regions, and also similarity in phosph and dephosph rates, I am borrowing GAP-43 kinetic info. See Alexander et al JBC 262:13 6108-6113 1987


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