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Molecule Parameter List for GTP-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 | MAPK_network_ 2003 | 50 | Network | Shared_Object_MAPK_network_2003, PKC, PLA2, PLCbeta, Gq, MAPK, Ras, EGFR, Sos, PLC_g, CaMKII, CaM, PP1, PP2B, PKA, AC | This is a network model of many pathways present at the neuronal synapse. The network has properties of temporal tuning as well as steady-state computational properties. In its default form the network is bistable.Bhalla US Biophys J. 2004 Aug;87(2):745-53 |
GTP-Ras acting as a Molecule in MAPK_network_2003 Network
Name | Accession Name | Pathway Name | Initial Conc. (uM) | Volume (fL) | Buffered | GTP-Ras | MAPK_network_ 2003 Accession No. : 50 | Ras Pathway No. : 212 | 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-Ras acting as a Substrate for an Enzyme in MAPK_network_2003 Network
Enzyme Molecule / Enzyme Activity | Accession Name | Pathway Name | Km (uM) | kcat (s^-1) | Ratio | Enzyme Type | Reagents | GAP / GAP-inact-ras | MAPK_network_ 2003 Accession No. : 50 | Ras Pathway No. : 212 | 1.01039 | 10 | 4 | explicit E-S complex | Substrate GTP-Ras
Product GDP-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-Ras acting as a Product of an Enzyme in MAPK_network_2003 Network
| Enzyme Molecule / Enzyme Activity | Accession Name | Pathway Name | Km (uM) | kcat (s^-1) | Ratio | Enzyme Type | Reagents | 1 | GEF-Gprot-bg / GEF-bg_act-ras | MAPK_network_ 2003 Accession No. : 50 | Ras Pathway No. : 212 | 0.505051 | 0.02 | 4 | explicit E-S complex | Substrate GDP-Ras
Product GTP-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 | GEF* / GEF*-act-ras | MAPK_network_ 2003 Accession No. : 50 | Ras Pathway No. : 212 | 0.505051 | 0.02 | 4 | explicit E-S complex | Substrate GDP-Ras
Product GTP-Ras
| | Kinetics same as GEF-bg-act-ras | 3 | CaM-GEF / CaM-GEF-act-ras | MAPK_network_ 2003 Accession No. : 50 | Ras Pathway No. : 212 | 0.505051 | 0.02 | 4 | explicit E-S complex | Substrate GDP-Ras
Product GTP-Ras
| | Kinetics same as GEF-bg_act-ras | 4 | Shc*.Sos.Grb2 / Sos.Ras_GEF | MAPK_network_ 2003 Accession No. : 50 | Shared_Object_ MAPK_network_ 2003 Pathway No. : 206 | 0.505051 | 0.02 | 4 | explicit E-S complex | Substrate GDP-Ras
Product GTP-Ras
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GTP-Ras acting as a Substrate in a reaction in MAPK_network_2003 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-act-craf | MAPK_network_ 2003 Accession No. : 50 | Shared_Object_ MAPK_network_ 2003 Pathway No. : 206 | 24 (uM^-1 s^-1) | 0.5 (s^-1) | Kd(bf) = 0.0208(uM) | - | Substrate GTP-Ras craf-1*
Product Raf-GTP-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 (I don't.... | 2 | Ras-intrinsic-GT Pase | MAPK_network_ 2003 Accession No. : 50 | Ras Pathway No. : 212 | 0.0001 (s^-1) | 0 (s^-1) | - | - | Substrate GTP-Ras
Product GDP-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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