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

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Reaction List for pathway CaM (Pathway Number 81)

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-Ca0.465
(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. Stemmer and Klee 1994 Biochem 33:6859-6866 kb/kf =21.5 * 6e5 so kf = 7.75e-7, kb = 10
2 CaM-TR2-bind-Ca72
(uM^-2 s^-1)
72
(s^-1)
Kd(af) = 1(uM)-CaM
Ca
Ca
CaM-TR2-Ca2
  We use the Martin et al 1985 Eur J Biochem 151(3):543-550 rates here, plus the Drabikowski and Brzeska 1982 JBC 257(19):11584-11590 binding consts. All are scaled by 3X to cell temperature. kf = 2e-10 kb = 72 Stemmer & Klee 1994 Biochem 33:6859-6866 have values of : K1=.9, K2=1.1. Assume 1.0uM for both
3 CaM-TR2-Ca2-bind
-Ca
3.6
(uM^-1 s^-1)
10
(s^-1)
Kd(bf) = 2.7778(uM)-CaM-TR2-Ca2
Ca
CaM-Ca3
  Stemmer and Klee 1994 Biochem 33:6859-6866 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
0.005
(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 estimate 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
0.3
(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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