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Molecule Parameter List for Ca | The statistics table lists the distribution of a molecule acting either as a substrate, product, enzyme or as a molecule within the network.
The text color of a molecule is highlighted by  color. | | Statistics |
Accession and Pathway Details | |
| Accession Name | Accession No. | Accession Type | Pathway Link | Ajay_Bhalla_
2007_Bistable | 79 | Network |
Shared_Object_Ajay_Bhalla_2007_Bistable, PKC, PLA2,
MAPK, Ras, CaM | This is a model of ERKII signaling which is bistable due to feedback. The feedback occurs through ERKII phosphorylation of phospholipase A2 (PLA2), leading to increased production of arachidonic acid (AA), which activates protein kinase C (PKC) which activates c-Raf which is upstream of ERKII.
The model is a highly simplified variant of more detailed bistable models of MAPK signaling (Bhalla US, Iyengar R. Science. 1999 Jan 15;283(5400):381-7, Ajay SM, Bhalla US. Eur J Neurosci. 2004 Nov;20(10):2671-80) |
Ca acting as a Molecule in Ajay_Bhalla_2007_Bistable Network
Ca acting as a Substrate in a reaction in Ajay_Bhalla_2007_Bistable Network
| 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 reaction are not consider. |
| | Name | Accession Name | Pathway Name | Kf | Kb | Kd | tau | Reagents | | 1 | PKC-act-by-Ca | Ajay_Bhalla_
2007_Bistable
Accession No. : 79 | PKC
Pathway No. : 364 | 0.6
(uM^-1 s^-1) | 0.5
(s^-1) | Kd(bf) = 0.8333(uM) | - | Substrate
Ca
PKC-cytosolic
Product
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 | | 2 | PLA2-Ca-act | Ajay_Bhalla_
2007_Bistable
Accession No. : 79 | PLA2
Pathway No. : 365 | 1
(uM^-1 s^-1) | 0.1
(s^-1) | Kd(bf) = 0.1(uM) | - | Substrate
Ca
PLA2-cytosolic
Product
PLA2-Ca*
| | | Leslie and Channon BBA 1045 (1990) 261-270 fig6 pp267. | | 3 | PLA2*-Ca-act | Ajay_Bhalla_
2007_Bistable
Accession No. : 79 | PLA2
Pathway No. : 365 | 6
(uM^-1 s^-1) | 0.1
(s^-1) | Kd(bf) = 0.0167(uM) | - | Substrate
Ca
PLA2*
Product
PLA2*-Ca
| | | To start off, same kinetics as the PLA2-Ca-act direct pathway. Oops ! Missed out the Ca input to this pathway first time round. Let's raise the forward rate about 3x to 5e-6. This will let us reduce the rather high rates we have used for the kenz on PLA2*-Ca. In fact, it may be that the rates are not that different, just that this pathway for getting the PLA2 to the memb is more efficien.... | | 4 | CaM-TR2-bind-Ca | Ajay_Bhalla_
2007_Bistable
Accession No. : 79 | CaM
Pathway No. : 368 | 72.0009
(uM^-2 s^-1) | 72
(s^-1) | Kd(af) = 1(uM) | - | Substrate
Ca
Ca
CaM
Product
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 !).... | | 5 | CaM-TR2-Ca2-bind
-Ca | Ajay_Bhalla_
2007_Bistable
Accession No. : 79 | CaM
Pathway No. : 368 | 3.6
(uM^-1 s^-1) | 10
(s^-1) | Kd(bf) = 2.7778(uM) | - | Substrate
Ca
CaM-TR2-Ca2
Product
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 | | 6 | CaM-Ca3-bind-Ca | Ajay_Bhalla_
2007_Bistable
Accession No. : 79 | CaM
Pathway No. : 368 | 0.465
(uM^-1 s^-1) | 10
(s^-1) | Kd(bf) = 21.5053(uM) | - | Substrate
Ca
CaM-Ca3
Product
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 |
Ca acting as a Product in a reaction in Ajay_Bhalla_2007_Bistable Network
| 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 reaction are not consider. |
| Database compilation and code copyright (C) 2022, Upinder S. Bhalla and NCBS/TIFR
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