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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 | Differential syn thesis of mRNA | 95 | 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 Differential synthesis of mRNA Network
Name | Accession Name | Pathway Name | Initial Conc. (uM) | Volume (fL) | Buffered | GTP_dash_Ras | Differential syn thesis of mRNA Accession No. : 95 | kinetics Pathway No. : 1115 | 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 Differential synthesis of mRNA Network
Enzyme Molecule / Enzyme Activity | Accession Name | Pathway Name | Km (uM) | kcat (s^-1) | Ratio | Enzyme Type | Reagents | GAP / GAP_dash_inact_ dash_ras
| Differential syn thesis of mRNA Accession No. : 95 | kinetics Pathway No. : 1115 | 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 Differential synthesis of mRNA 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
| Differential syn thesis of mRNA Accession No. : 95 | kinetics Pathway No. : 1115 | 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
| Differential syn thesis of mRNA Accession No. : 95 | kinetics Pathway No. : 1115 | 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
| Differential syn thesis of mRNA Accession No. : 95 | kinetics Pathway No. : 1115 | 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 | Differential syn thesis of mRNA Accession No. : 95 | kinetics Pathway No. : 1115 | 0.0505 | 0.2 | 4 | explicit E-S complex | Substrate GDP_dash_Ras
Product GTP_dash_Ras
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GTP_dash_Ras acting as a Substrate in a reaction in Differential synthesis of mRNA 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 | Differential syn thesis of mRNA Accession No. : 95 | kinetics Pathway No. : 1115 | 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 | Differential syn thesis of mRNA Accession No. : 95 | kinetics Pathway No. : 1115 | 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 | Differential syn thesis of mRNA Accession No. : 95 | kinetics Pathway No. : 1115 | 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 | Differential syn thesis of mRNA Accession No. : 95 | kinetics Pathway No. : 1115 | 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 |
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