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Molecule Parameter List for GTP_dash_Ras | 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 | | mRNA synthesis | 94 | Network |
kinetics, compartment_1, compartment_2 | | The model consists of three major pathways: Calcium-calmodulin dependent protein kinase IV (CaMKIV), Mitogen-activated protein kinase (MAPK) and Protein Phosphatase 1 (PP1). Each of these converged on CREB activation. We also modeled further interactions with Transducer of regulated CREB activity 1 (TORC1) and the protein kinase A (PKA) pathway. |
GTP_dash_Ras acting as a Molecule in mRNA synthesis Network
| Name | Accession Name | Pathway Name | Initial Conc.
(uM) | Volume
(fL) | Buffered | | GTP_dash_Ras | mRNA synthesis
Accession No. : 94 | kinetics
Pathway No. : 1112 | 0 | 1000 | No | | Only a very small fraction (7% unstim, 15% stim) of ras is GTP-bound. Gibbs et al JBC 265(33) 20437 |
GTP_dash_Ras acting as a Substrate for an Enzyme in mRNA synthesis Network
Enzyme Molecule /
Enzyme Activity | Accession Name | Pathway Name | Km (uM) | kcat (s^-1) | Ratio | Enzyme Type | Reagents | GAP /
GAP_dash_inact_
dash_ras
| mRNA synthesis
Accession No. : 94 | kinetics
Pathway No. : 1112 | 1.0104 | 10 | 4 | explicit E-S complex | Substrate
GTP_dash_Ras
Product
GDP_dash_Ras
| | From Eccleston et al JBC 268(36)pp27012-19 get Kd < 2uM, kcat - 10/sec From Martin et al Cell 63 843-849 1990 get Kd ~ 250 nM, kcat = 20/min I will go with the Eccleston figures as there are good error bars (10%). In general the values are reasonably close. k1 = 1.666e-3/sec, k2 = 1000/sec, k3 = 10/sec (note k3 is rate-limiting) 5 Nov 2002: Changed ratio term to 4 from 100. Now we have k1=8.25e-5; k2=40, k3=10. k3 is still rate-limiting. |
GTP_dash_Ras acting as a Product of an Enzyme in mRNA synthesis Network
| | Enzyme Molecule /
Enzyme Activity | Accession Name | Pathway Name | Km (uM) | kcat (s^-1) | Ratio | Enzyme Type | Reagents | | 1 | GEF_dash_Gprot_
dash_bg /
GEF_dash_bg_
act_dash_ras
| mRNA synthesis
Accession No. : 94 | kinetics
Pathway No. : 1112 | 0.5051 | 0.02 | 4 | explicit E-S complex | Substrate
GDP_dash_Ras
Product
GTP_dash_Ras
| | | Kinetics based on the activation of Gq by the receptor complex in the Gq model (in turn based on the Mahama and Linderman model) k1 = 2e-5, k2 = 1e-10, k3 = 10 (I do not know why they even bother with k2). Lets put k1 at 2e-6 to get a reasonable equilibrium More specific values from, eg.g: Orita et al JBC 268(34) 25542-25546 from rasGRF and smgGDS: k1=3.3e-7; k2 = 0.08, k3 = 0.02 | | 2 | CaM_dash_GEF /
CaM_dash_GEF_
dash_act_dash_
ras
| mRNA synthesis
Accession No. : 94 | kinetics
Pathway No. : 1112 | 0.5051 | 0.02 | 4 | explicit E-S complex | Substrate
GDP_dash_Ras
Product
GTP_dash_Ras
| | | Kinetics same as GEF-bg_act-ras | | 3 | GEF_star /
GEF_star_dash_
act_dash_ras
| mRNA synthesis
Accession No. : 94 | kinetics
Pathway No. : 1112 | 0.5051 | 0.02 | 4 | explicit E-S complex | Substrate
GDP_dash_Ras
Product
GTP_dash_Ras
| | | Kinetics same as GEF-bg-act-ras | | 4 | Shc_
star.Sos.Grb2 /
Sos.Ras_GEF | mRNA synthesis
Accession No. : 94 | kinetics
Pathway No. : 1112 | 0.0505 | 0.2 | 4 | explicit E-S complex | Substrate
GDP_dash_Ras
Product
GTP_dash_Ras
| | | |
GTP_dash_Ras acting as a Substrate in a reaction in mRNA synthesis 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 | Ras_dash_act_
dash_unphosph_
dash_raf | mRNA synthesis
Accession No. : 94 | kinetics
Pathway No. : 1112 | 6
(uM^-1 s^-1) | 1
(s^-1) | Kd(bf) = 0.1667(uM) | - | Substrate
GTP_dash_Ras
craf_dash_1
Product
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. | | 2 | Ras_dash_act_
dash_craf | mRNA synthesis
Accession No. : 94 | kinetics
Pathway No. : 1112 | 9.9996
(uM^-1 s^-1) | 0.5
(s^-1) | Kd(bf) = 0.05(uM) | - | Substrate
GTP_dash_Ras
craf_dash_1_
star
Product
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. | | 3 | Ras_dash_act_
dash_braf | mRNA synthesis
Accession No. : 94 | kinetics
Pathway No. : 1112 | 60
(uM^-1 s^-1) | 0.5
(s^-1) | Kd(bf) = 0.0083(uM) | - | Substrate
GTP_dash_Ras
bRaf
Product
braf_dash_GTP_
dash_Ras
| | | | | 4 | Ras_dash_
intrinsic_dash_
GTPase | mRNA synthesis
Accession No. : 94 | kinetics
Pathway No. : 1112 | 0.0001
(s^-1) | 0
(s^-1) | - | - | Substrate
GTP_dash_Ras
Product
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 |
| Database compilation and code copyright (C) 2022, Upinder S. Bhalla and NCBS/TIFR
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