| | Name | Accession Name | Pathway Name | Kf | Kb | Kd | tau | Reagents |
| 1 | PKC-act-by-Ca | Synaptic_
Network
Accession No. : 16 | PKC
Pathway No. : 71 | 0.6
(uM^-1 s^-1) | 0.5
(s^-1) | Kd(bf) = 0.8333(uM) | - | Substrate
Ca
PKC-cytosolic
Product
PKC-Ca
|
| | This Kd is a straightforward result from the Schaechter and Benowitz 1993 J Neurosci 13(10):4361 curves. The time-course is based on the known rapid activation of PKC and also the fact that Ca association with proteins is typically quite fast. My guess is that this tau of 2 sec is quite conservative and the actualy rate may be much faster. The parameter is quite insensitive for most stimuli. |
| 2 | PLA2-Ca-act | Synaptic_
Network
Accession No. : 16 | PLA2
Pathway No. : 72 | 1
(uM^-1 s^-1) | 0.1
(s^-1) | Kd(bf) = 0.1(uM) | - | Substrate
Ca
PLA2-cytosolic
Product
PLA2-Ca*
|
| | Direct activation of PLA2 by Ca. From Leslie and Channon BBA 1045 (1990) 261-270 fig6 pp267. |
| 3 | PLA2*-Ca-act | Synaptic_
Network
Accession No. : 16 | PLA2
Pathway No. : 72 | 6
(uM^-1 s^-1) | 0.1
(s^-1) | Kd(bf) = 0.0167(uM) | - | Substrate
Ca
PLA2*
Product
PLA2*-Ca
|
| | Nemenoff et al 1993 JBC 268:1960 report a 2X to 4x activation of PLA2 by MAPK, which seems dependent on Ca as well. This reaction represents this activation. Rates are scaled to give appropriate fold activation. |
| 4 | Act-PLC-Ca | Synaptic_
Network
Accession No. : 16 | PLCbeta
Pathway No. : 73 | 3
(uM^-1 s^-1) | 1
(s^-1) | Kd(bf) = 0.3333(uM) | - | Substrate
Ca
PLC
Product
PLC-Ca
|
| | Affinity for Ca = 1uM without AlF, 0.1 with: from Smrcka et al science 251 pp 804-807 1991 Assigned affinity to a Kd of 0.333 to maintain detailed balance. |
| 5 | PLC-Gq-bind-Ca | Synaptic_
Network
Accession No. : 16 | PLCbeta
Pathway No. : 73 | 30
(uM^-1 s^-1) | 1
(s^-1) | Kd(bf) = 0.0333(uM) | - | Substrate
Ca
PLC-Gq
Product
PLC-Ca-Gq
|
| | this step has a high affinity of 0.1 uM for Ca, from Smrcka et al 1991 Science 251:804-807 so kf /kb = 1/6e4 = 1.666e-5:1. See the Act-PLC-by-Gq reaction. Raised kf to 5e-5 based on match to conc-eff curves from Smrcka et al. |
| 6 | Ca_act_PLC_g | Synaptic_
Network
Accession No. : 16 | PLC_g
Pathway No. : 79 | 180
(uM^-1 s^-1) | 10
(s^-1) | Kd(bf) = 0.0556(uM) | - | Substrate
Ca
PLC_g
Product
Ca.PLC_g
|
| | Nice curves from Homma et al JBC 263:14 6592-6598 1988 Fig 5c. The activity falls above 10 uM, but that is too high to reach physiologically anyway, so we'll ignore the higher pts and match the lower ones only. Half-max at 1 uM. But Wahl et al JBC 267:15 10447-10456 1992 have half-max at 56 nM which is what I'll use. |
| 7 | Ca_act_PLC_g* | Synaptic_
Network
Accession No. : 16 | PLC_g
Pathway No. : 79 | 12
(uM^-1 s^-1) | 10
(s^-1) | Kd(bf) = 0.8333(uM) | - | Substrate
Ca
PLC_G*
Product
Ca.PLC_g*
|
| | Again, we refer to Homma et al and Wahl et al, for preference using Wahl et al JBC 267(15):10447-10456 1992. Half-Max of the phosph form is at 316 nM. Use kb of 10 as this is likely to be pretty fast. As we are phosphorylating the Ca-bound form, equils have shifted. kf should now be 2e-5 (Kf = 12) to match the reported half-max. |
| 8 | CaM-TR2-bind-Ca | Synaptic_
Network
Accession No. : 16 | CaM
Pathway No. : 81 | 72
(uM^-2 s^-1) | 72
(s^-1) | Kd(af) = 1(uM) | - | Substrate
Ca
Ca
CaM
Product
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 |
| 9 | CaM-TR2-Ca2-bind
-Ca | Synaptic_
Network
Accession No. : 16 | CaM
Pathway No. : 81 | 3.6
(uM^-1 s^-1) | 10
(s^-1) | Kd(bf) = 2.7778(uM) | - | Substrate
Ca
CaM-TR2-Ca2
Product
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 |
| 10 | CaM-Ca3-bind-Ca | Synaptic_
Network
Accession No. : 16 | CaM
Pathway No. : 81 | 0.465
(uM^-1 s^-1) | 10
(s^-1) | Kd(bf) = 21.5054(uM) | - | Substrate
Ca
CaM-Ca3
Product
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 |
| 11 | Ca-bind-CaNAB-Ca
2 | Synaptic_
Network
Accession No. : 16 | PP2B
Pathway No. : 83 | 3.6
(uM^-2 s^-1) | 1
(s^-1) | Kd(af) = 0.527(uM) | - | Substrate
Ca
Ca
CaNAB-Ca2
Product
CaNAB-Ca4
|
| | This process is probably much more complicated and involves CaM. However, as I can't find detailed info I am bundling this into a single step. Based on Steemer and Klee 1994 Biochem 33:6859-6866, this specific parm on pg 6863, the Kact is 0.5 uM. Assume binding is fast, 1 sec. |
| 12 | Ca-bind-CaNAB | Synaptic_
Network
Accession No. : 16 | PP2B
Pathway No. : 83 | 10008
(uM^-2 s^-1) | 1
(s^-1) | Kd(af) = 0.01(uM) | - | Substrate
Ca
Ca
CaNAB
Product
CaNAB-Ca2
|
| | going on the experience with CaM, we put the fast (high affinity) sites first. We only know (Stemmer and Klee) that the affinity is < 70 nM. Assuming 10 nM at first. This doesn't really matter much because it will always be bound at physiological Ca. |
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