| | Name | Kf | Kb | Kd | tau | Substrate | Product |
| 1 |
Autophos_TrKB | 0.02
(s^-1) | 0
(s^-1) | - | - | BDNF_TrkB2_clx
| BDNF_TrkB2_
star_clx
|
| | |
| 2 |
bg_dash_act_
dash_GEF | 6
(uM^-1 s^-1) | 1
(s^-1) | Kd(bf) = 0.1667(uM) | - | inact_dash_GEF
BetaGamma
| GEF_dash_Gprot_
dash_bg
|
| | SoS/GEF is present at 50 nM ie 3e4/cell. BetaGamma maxes out at 9e4. Assume we have 1/3 of the GEF active when the BetaGamma is 1.5e4. so 1e4 * kb = 2e4 * 1.5e4 * kf, so kf/kb = 3e-5. The rate of this equil should be reasonably fast, say 1/sec |
| 3 |
B_dash_Raf_
bind_Rap1GTP | 60
(uM^-1 s^-1) | 0.5
(s^-1) | Kd(bf) = 0.0083(uM) | - | Rap1GTP
bRaf
| bRaf_Rap1GTP
|
| | |
| 4 |
C1_dash_binding | 799.02
(uM^-1 s^-1) | 0.186
(s^-1) | Kd(bf) = 0.0002(uM) | - | PKA_dash_active
R2
| R2C1
|
| | PMID: 11110787 |
| 5 |
C2_dash_binding | 799.02
(uM^-1 s^-1) | 0.186
(s^-1) | Kd(bf) = 0.0002(uM) | - | PKA_dash_active
R2C1
| R2C2
|
| | |
| 6 |
C3G_bind_CRK | 1
(uM^-1 s^-1) | 0.002
(s^-1) | Kd(bf) = 0.002(uM) | - | C3G
CRK
| CRK_C3G
|
| | |
| 7 |
CaMCa3_dash_
bind_dash_CaNAB | 2.238
(uM^-1 s^-1) | 1
(s^-1) | Kd(bf) = 0.4468(uM) | - | CaM_dash_Ca3
CaNAB_dash_Ca4
| CaMCa3_dash_
CaNAB
|
| | |
| 8 |
CaMCa4_dash_
bind_dash_CaNAB | 600
(uM^-1 s^-1) | 1
(s^-1) | Kd(bf) = 0.0017(uM) | - | CaM_dash_Ca4
CaNAB_dash_Ca4
| CaMCa4_dash_
CaNAB
|
| | |
| 9 |
CaMKIVcomplx | 0.0133
(uM^-1 s^-1) | 0.01
(s^-1) | Kd(bf) = 0.7508(uM) | - | CaM_dash_Ca4
CaMKIVc
| CaMKIV_CaM_Ca_c
|
| | Kd from PMID: 9705275 |
| 10 |
CaMKIVimport | 0.0009
(s^-1) | 0.0026
(s^-1) | Keq = 2.8778(uM) | 285.714sec | pCaMKIV_CaM_Ca_
c
| pCaMKIV_CaM_Ca_
c
|
| | |
| 11 |
CaMKKcomplx | 4.05
(uM^-1 s^-1) | 0.02
(s^-1) | Kd(bf) = 0.0049(uM) | - | CaM_dash_Ca4
CaMKK_c
| CaMKK_CaM_Ca_c
|
| | Kd from PMID: 9705275 |
| 12 |
cAMP_dash_bind_
dash_site_dash_
A1 | 75
(uM^-1 s^-1) | 110
(s^-1) | Kd(bf) = 1.4667(uM) | - | R2C2_dash_cAMP2
cAMP
| R2C2_dash_cAMP3
|
| | |
| 13 |
cAMP_dash_bind_
dash_site_dash_
A2 | 75
(uM^-1 s^-1) | 32.5
(s^-1) | Kd(bf) = 0.4333(uM) | - | R2C2_dash_cAMP3
cAMP
| R2C2_dash_cAMP4
|
| | |
| 14 |
cAMP_dash_bind_
dash_site_dash_
B1 | 54
(uM^-1 s^-1) | 33
(s^-1) | Kd(bf) = 0.6111(uM) | - | R2C2
cAMP
| R2C2_dash_cAMP
|
| | |
| 15 |
cAMP_dash_bind_
dash_site_dash_
B2 | 54
(uM^-1 s^-1) | 33
(s^-1) | Kd(bf) = 0.6111(uM) | - | R2C2_dash_cAMP
cAMP
| R2C2_dash_cAMP2
|
| | |
| 16 |
CaM_bind_PDE1 | 720
(uM^-1 s^-1) | 5
(s^-1) | Kd(bf) = 0.0069(uM) | - | CaM_dash_Ca4
PDE1
| CaM.PDE1
|
| | |
| 17 |
CaM_dash_bind_
dash_AC1 | 49.9998
(uM^-1 s^-1) | 1
(s^-1) | Kd(bf) = 0.02(uM) | - | CaM_dash_Ca4
AC1
| AC1_dash_CaM
|
| | |
| 18 |
CaM_dash_bind_
dash_Ca | 8.4846
(uM^-1 s^-1) | 8.4853
(s^-1) | Kd(bf) = 1.0001(uM) | - | CaM
Ca
| CaM_dash_Ca
|
| | 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 !) 19 May 2006. Splitting the old CaM-TR2-bind-Ca reaction into two steps, each binding 1 Ca. This improves numerical stability and is conceptually better too. Overall rates are the same, so each kf and kb is the square root of the earlier ones. So kf = 1.125e-4, kb = 8.4853 |
| 19 |
CaM_dash_bind_
dash_GEF | 60
(uM^-1 s^-1) | 1
(s^-1) | Kd(bf) = 0.0167(uM) | - | CaM_dash_Ca4
inact_dash_GEF
| CaM_dash_GEF
|
| | We have no numbers for this. It is probably between the two extremes represented by the CaMKII phosph states, and I have used guesses based on this. kf=1e-4 kb=1 The reaction is based on Farnsworth et al Nature 376 524-527 1995 |
| 20 |
CaM_dash_Ca2_
dash_bind_dash_
Ca | 3.6001
(uM^-1 s^-1) | 10
(s^-1) | Kd(bf) = 2.7777(uM) | - | CaM_dash_Ca2
Ca
| CaM_dash_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 |
| 21 |
CaM_dash_Ca2_
dash_bind_dash_
CaNAB | 0.24
(uM^-1 s^-1) | 1
(s^-1) | Kd(bf) = 4.1667(uM) | - | CaM_dash_Ca2
CaNAB_dash_Ca4
| CaMCa2_dash_
CANAB
|
| | Disabled. See notes for PP2B7.g |
| 22 |
CaM_dash_Ca3_
dash_bind_dash_
Ca | 0.465
(uM^-1 s^-1) | 10
(s^-1) | Kd(bf) = 21.5051(uM) | - | CaM_dash_Ca3
Ca
| CaM_dash_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 |
| 23 |
CaM_dash_Ca_
dash_bind_dash_
Ca | 8.4846
(uM^-1 s^-1) | 8.4853
(s^-1) | Kd(bf) = 1.0001(uM) | - | CaM_dash_Ca
Ca
| CaM_dash_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 !) 19 May 2006. Splitting the old CaM-TR2-bind-Ca reaction into two steps, each binding 1 Ca. This improves numerical stability and is conceptually better too. Overall rates are the same, so each kf and kb is the square root of the earlier ones. So kf = 1.125e-4, kb = 8.4853 |
| 24 |
Ca_dash_bind_
dash_CaNAB | 10008360
(uM^-2 s^-1) | 1
(s^-1) | Kd(af) = 0.0003(uM) | - | Ca
Ca
CaNAB
| CaNAB_dash_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, we get kf = 2.78e-8, kb = 1. Try 20 nM. kf = 7e-9, kb = 1 |
| 25 |
Ca_dash_bind_
dash_CaNAB_
dash_Ca2 | 3599.928
(uM^-2 s^-1) | 1
(s^-1) | Kd(af) = 0.0167(uM) | - | Ca
Ca
CaNAB_dash_Ca2
| CaNAB_dash_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 pg 6863, the Kact is 0.5 uM. kf/kb = 1/(0.5 * 6e5)^2 = 1.11e-11 |
| 26 |
Ca_stoch | 100
(s^-1) | 100
(s^-1) | Keq = 1(uM) | 0.005sec | Ca_input
| Ca
|
| | |
| 27 |
Cbl_dephospho | 10
(s^-1) | 0.01
(s^-1) | Keq = 0.001(uM) | 0.1sec | Cbl_star
| Cbl
|
| | |
| 28 |
CRK_C3G_Cbl_
star | 1
(uM^-1 s^-1) | 0.2
(s^-1) | Kd(bf) = 0.2(uM) | - | CRK_C3G
Cbl_star
| CRK_C3G_Cbl_
star_clx
|
| | |
| 29 |
dephosph_dash_
AC2 | 0.1
(s^-1) | 0
(s^-1) | - | - | AC2_star
| AC2
|
| | |
| 30 |
dephosph_dash_
GAP | 0.1
(s^-1) | 0
(s^-1) | - | - | GAP_star
| GAP
|
| | Assume a reasonably good rate for dephosphorylating it, 1/sec |
| 31 |
dephosph_dash_
GEF | 1
(s^-1) | 0
(s^-1) | - | - | GEF_star
| inact_dash_GEF
|
| | |
| 32 |
dephosph_dash_
inact_dash_GEF_
star | 1
(s^-1) | 0
(s^-1) | - | - | inact_dash_GEF_
star
| inact_dash_GEF
|
| | |
| 33 |
dephosph_dash_
PDE | 0.1
(s^-1) | 0
(s^-1) | - | - | cAMP_dash_PDE_
star
| cAMP_dash_PDE
|
| | |
| 34 |
dephosph_Sos | 0.001
(s^-1) | 0.1
(s^-1) | Keq = 100(uM) | 9.901sec | Sos_star
| Sos
|
| | |
| 35 |
Dimeriz_TrKB | 1
(uM^-1 s^-1) | 0.02
(s^-1) | Kd(bf) = 0.02(uM) | - | TrKB
BDNF_TrkB_clx
| BDNF_TrkB2_clx
|
| | |
| 36 |
dissociation | 0.0005
(s^-1) | 0.0001
(uM^-1 s^-1) | Kd(cb) = 0.2(uM) | - | R2_dash_cAMP4
| R2
cAMP
|
| | |
| 37 |
dissoc_dash_
PP1_dash_I1 | 1
(s^-1) | 0
(uM^-1 s^-1) | - | - | PP1_dash_I1
| I1
PP1_dash_
active_c
|
| | Let us assume that the equil in this case is very far over to the right. This is probably safe. |
| 38 |
Grb2_bind_Sos | 0.25
(uM^-1 s^-1) | 0.0168
(s^-1) | Kd(bf) = 0.0672(uM) | - | Grb2
Sos
| Sos.Grb2
|
| | |
| 39 |
Grb2_bind_Sos_
star | 0.025
(uM^-1 s^-1) | 0.0168
(s^-1) | Kd(bf) = 0.672(uM) | - | Grb2
Sos_star
| Sos_star.Grb2
|
| | |
| 40 |
Inact_dash_PP1 | 499.974
(uM^-1 s^-1) | 0.1
(s^-1) | Kd(bf) = 0.0002(uM) | - | I1_star
PP1_dash_
active_c
| PP1_dash_I1_
star
|
| | K inhib = 1nM from Cohen Ann Rev Bioch 1989, 4 nM from Foukes et al Assume 2 nM. kf /kb = 8.333e-4 |
| 41 |
inhib_dash_PKA | 60
(uM^-1 s^-1) | 1
(s^-1) | Kd(bf) = 0.0167(uM) | - | PKA_dash_active
PKA_dash_
inhibitor
| inhibited_dash_
PKA
|
| | |
| 42 |
intrinsic_
GTPase | 0.0001
(s^-1) | 0
(s^-1) | - | - | Rap1GTP
| Rap1GDP
|
| | |
| 43 |
Ligand_binding | 1.0001
(uM^-1 s^-1) | 0.05
(s^-1) | Kd(bf) = 0.05(uM) | - | TrKB
BDNF
| BDNF_TrkB_clx
|
| | |
| 44 |
LR_cycling | 0.001
(s^-1) | 0.001
(s^-1) | Keq = 1(uM) | 500sec | Int_BDNF_TrKB2_
star_clx
| TrKB
|
| | |
| 45 |
LR_Internalize | 0.01
(s^-1) | 0
(uM^-1 s^-1) | - | - | BDNF_TrkB2_
star_clx
| Int_BDNF_TrKB2_
star_clx
Int_BDNF_TrKB2_
star_clx
|
| | |
| 46 |
PKAimport | 0.0003
(s^-1) | 0.0005
(s^-1) | Keq = 1.5164(uM) | 1250sec | PKA_dash_active
| PKA_dash_active
|
| | |
| 47 |
PLC_g_p_
dephospho | 0.07
(s^-1) | 0
(s^-1) | - | - | PLC_g_star
| PLC_g
|
| | |
| 48 |
PP1_transport | 0.003
(s^-1) | 0.0011
(s^-1) | Keq = 0.37(uM) | 243.902sec | PP1_dash_I1
| PP1_dash_I1
|
| | |
| 49 |
Ras_dash_act_
dash_braf | 60
(uM^-1 s^-1) | 0.5
(s^-1) | Kd(bf) = 0.0083(uM) | - | bRaf
GTP_dash_Ras
| braf_dash_GTP_
dash_Ras
|
| | |
| 50 |
Ras_dash_act_
dash_craf | 9.9996
(uM^-1 s^-1) | 0.5
(s^-1) | Kd(bf) = 0.05(uM) | - | craf_dash_1_
star
GTP_dash_Ras
| Raf_star_dash_
GTP_dash_Ras
|
| | Assume the binding is fast and limited only by the amount of Ras* available. So kf=kb/[craf-1] If kb is 1/sec, then kf = 1/0.2 uM = 1/(0.2 * 6e5) = 8.3e-6 Later: Raise it by 10 X to 4e-5 From Hallberg et al JBC 269:6 3913-3916 1994, 3% of cellular Raf is complexed with Ras. So we raise kb 4x to 4 This step needed to memb-anchor and activate Raf: Leevers et al Nature 369 411-414 May 16, 2003 Changed Ras and Raf to synaptic levels, an increase of about 2x for each. To maintain the percentage of complexed Raf, reduced the kf by 2.4 fold to 10. |
| 51 |
Ras_dash_act_
dash_unphosph_
dash_raf | 6
(uM^-1 s^-1) | 1
(s^-1) | Kd(bf) = 0.1667(uM) | - | craf_dash_1
GTP_dash_Ras
| Raf_dash_GTP_
dash_Ras
|
| | 18 May 2003. This reaction is here to provide basal activity for MAPK as well as the potential for direct EGF stimulus without PKC activation. Based on model from FB/fb28c.g: the model used for MKP-1 turnover. The rates there were constrained by basal activity values. |
| 52 |
Ras_dash_
intrinsic_dash_
GTPase | 0.0001
(s^-1) | 0
(s^-1) | - | - | GTP_dash_Ras
| GDP_dash_Ras
|
| | This is extremely slow (1e-4), but it is significant as so little GAP actually gets complexed with it that the total GTP turnover rises only by 2-3 X (see Gibbs et al, JBC 265(33) 20437-20422) and Eccleston et al JBC 268(36) 27012-27019 kf = 1e-4 |
| 53 |
Release_dash_C1 | 60
(s^-1) | 18
(uM^-1 s^-1) | Kd(cb) = 0.3(uM) | - | R2C2_dash_cAMP4
| PKA_dash_active
R2C_dash_cAMP4
|
| | |
| 54 |
Release_dash_C2 | 60
(s^-1) | 18
(uM^-1 s^-1) | Kd(cb) = 0.3(uM) | - | R2C_dash_cAMP4
| PKA_dash_active
R2_dash_cAMP4
|
| | |
| 55 |
RSK_
autophosphorylat
ion | 0.1
(s^-1) | 10
(s^-1) | Keq = 100(uM) | 0.099sec | pRSK
| ppRSK
|
| | |
| 56 |
Shc_bind_
Sos.Grb2 | 5
(uM^-1 s^-1) | 0.1
(s^-1) | Kd(bf) = 0.02(uM) | - | Sos.Grb2
Shc_star
| Shc_
star.Sos.Grb2
|
| | |
| 57 |
Shc_p_dephospho | 0.2
(s^-1) | 0
(s^-1) | - | - | Shc_star
| Shc
|
| | |
| 58 |
SIK2_dephosp | 0.1
(s^-1) | 0
(s^-1) | - | - | SIK2_star
| SIK2
|
| | |
| 59 |
Src_dephospho | 100
(s^-1) | 0.1
(s^-1) | Keq = 0.001(uM) | 0.01sec | Src_star
| Src
|
| | |
| 60 |
TORC1_import | 0.01
(s^-1) | 0
(s^-1) | Keq = 0.0037(uM) | - | TORC1c
| TORC1c
|
| | |
| 61 |
transport_MAPK | 0.0001
(s^-1) | 0.0011
(s^-1) | Keq = 11.1(uM) | 833.333sec | MAPK_star
| MAPK_star
|
| | |
| 62 |
transport_RSK2n | 0.001
(s^-1) | 0.0019
(s^-1) | Keq = 1.85(uM) | 344.828sec | active_RSK2
| active_RSK2
|
| | |
